RECENT ADVANCES IN THE DEFINITION OF THE MOLECULAR ALTERATIONS OCCURRING IN MULTIPLE MYELOMA MOLECULAR ALTERATIONS OCCURRING IN MM
Main Article Content
Keywords
Abstract
Multiple myeloma (MM) is a disorder of the monoclonal plasma cells and is the second most common hematologic malignancy. MM initiation and progression are dependent upon complex genomic abnormalities. The current pathogenic model of MM includes two types of primary events, represented by chromosome translocations or chromosome number alterations resulting in hyperdiploidy. These primary molecular events are observed both in MM and in monoclonal gammopathy, its premalignant precursor. Subsequent genetic events allow the progression of monoclonal gammopathy to MM and, together with primary events, contribute to the genetic complexity and heterogeneity of MM.
Newer therapies have considerably improved patient outcomes; however, MM remains an incurable disease and most patients experience multiple relapses.
The dramatic progresses achieved in the analysis of the heterogeneous molecular features of different MM patients allowed a comprehensive molecular classification of MM and the definition of an individualized prognostic model to predict an individual MM patient’s response to different therapeutic options. Despite these progresses, prognostic models fail to identify a significant proportion of patients destined to early relapse. Treatment strategies are increasingly. Based on disease biology, trials are enriched for high-risk MMs, whose careful definition and categorization requires DNA sequencing studies.
Keywords: Multiple Myeloma; Chromosome Abnormalities; Molecular Events; Mutations.
Downloads
Download data is not yet available.
Abstract 443
PDF Downloads 579
HTML Downloads 40
References
1. Atrash S, Robinson M, Slaugheter D, Aneralla A, Brown T, Robinson J, Ndiaye A, Sprouse C, Zhang Q, Symanoski JT, et al. Evolving changes in M-protein and hemoglobin as predictors for progression of smouldering multiple myeloma. Blood Cancer J 2018; 8: 107.
2. Rajkumar SV, Landgren O, Mateos MV. Smouldering multiple myeloma. Blood 2015; 125: 3069-3075.
3. Walker BA, Leone PE. Chiecchio L, Dickens NJ, Jenner MW, Boyd KD, Johnson DC, Gonzalez D, Dagrada GP, Protheroa R, et al. A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood 2010; 116: e56-65.
4. Barwick BG, Gupta VA, Verino PM, Boise LH. Cell of origin and genetic alterations in the pathogenesis of multiple myeloma. Front Immunol 2019; 10: 1121.
5. Samur AA, Minelli S, Shammas M, Falciniti M, Magrangeas F, Richardson PG, Moreau P, Attal M, Anderson KC, Parmigiani G, et al. Deciphering the chronology of copy number alterations in multiple myeloma. Blood Cancer 2019; 9: 39.
6. Maura F, Bolli N, Angelopoulos N, Dawson KJ, Leogmornlert D, Martincorena I, Mitchell TJ, Fullam A, Gonzalez S, Szalat R, et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun 2019; 10: 3835.
7. Shah V, Sherborne AL, Walker BA, Johnson DC, Boyle EM, Ellis S, Begum DB, Proszek PZ, Jones JR, Pawlyn C, et al. Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles in 1905 trial patients. Leukemia 2018; 32:102-110.
8. Barilà G, Bonaldi L, Grassi A, Martines A, Lico A, Macrì N, Nalio S, Pavan L, Berno T, Branca A, et al. Identification of the true hyperdiploid multiple myeloma subset by combining conventional karyotyping and FISH analysis. Blood Cancer J 2020; 10: 18.
9. Wang Y, Zhuang J, An G, Mao XH, Du C, Liu J, Fan H, Deng S, Xu Y, Sui W, et al. Prognostic impact of hyperploidy on multiple myeloma in the era of new agents. Blood 2020; 136(suppl.1): 20.
10. Samur MK, Samur AA, Fulciniti MT, Szalat R, Han T, Shammas M, Richardson P, Magrangeas F, Minvielle S, Corre J, et al. Genome-wide somatic alterations in multiple myeloma reveal a superior outcome group. J Clin Oncol 2020; 38: 3107-3118.
11. Pawlyn C, Melchor L, Murison A, Wardell CP, Brioli A, Boyle EM, Kaiser MF, Walker BA, Begum DB, Dahir NB, Proszek P, et al. Coexistent hyperploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH translocations. Blood 2015; 125: 831-840.
12. Wiedmeier-Nutor_JE, Bergsagel PL. Review of multiple myeloma genetics including effects on prognosis, response to treatment, and diagnostic workup. Life 2022; 22: 812.
13. Hanamura I, Iida S, Ueda R, Kuehl M, Cullraro C, Bergsagel L, Sawyer J, Barlogie B, Shaughnessy J. Identification of three novel chromosomal translocation partners involving the immunoglobulin loci in newly diagnosed myeloma and human myeloma cell lines. Blood 2005 ; 106 : 1552.
14. Hanamura I. Multiple myeloma with high-risk cytogenetics and its treatment approach. Int J Haematol 2022 ; 115 : 762-777.
15. Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J. Cyclin D regulation: an early and unifying pathogenic event in multiple myeloma. Blood 2005; 106: 296-303.
16. Bal S, Kumar SK, Fonseca R, Gay F, Hungria V, Dogan A, Costa LJ. Multiple myeloma with t(11;14): unique biology and evolving landscape. Am J Cancer Res 2022; 12: 2950-2965.
17. Ross JA, Avet-Loiseau H, Li X, Thiebaut-Millot R, Hader C. Genomic landscape of t(11;14) in multiple myeloma. Blood 2022; 140(suppl.1): 10092-10093.
18. Avet-Loiseau H, Thiébaut-Millot R, Li X, Ross JA, Hader C. t(11;14) status is stable between diagnosis and relapse, and concordant between detection methodologies based on fluorescence in situ hybridization and next-generation sequencing in patients with multiple myeloma. Haematologica 2024; in press.
19. Maura F, Rajanna AR, Ziccheddu B, Poos AM, Derkach A, Maclachlan K, Durante M, Diamond B, Papadimitriou M, Davies F, et al. Genomic classification and individualized prognosis in multiple myeloma. J Clin Oncol 2024; 42: 1229-1240.
20. Ziccheddu B, Da Vià MC, Lionetti M, Maeda A, Morlupi S, Dugo M, Todoerti K, Olivia S, D’Agostino M, Corradini P, et al. Functional impact of genomic complexity on the transcriptome of multiple myeloma. Clin Cancer Res 2021; 27: 6479-6490.
21. Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, Hungria V, Salwender H, Suzuki K, Kim I, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomized, double-blind, multicentre, phase 3 trial. Lancet Oncol 2020; 21: 1630-1642.
22. Mateos MV, Beksac M, Dismopoulos MA, et al. Results from the randomized, open-label phase 3 CANOVA study of venetoclax-dexamethasone versus pomalidomide-dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma. International Myeloma Society 2023 Annual Meeting. Abstract OA-25, September 2023.
23. Kaufman JL, Gasparetto C, Kovacsovics T, et al. Frist results from the randomized portion of a phase 2 study of venetoclax plus carfilzomib-dexamethasone vs carfilzomib-dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma. International Myeloma Society 2023 Annual Meeting. Abstract OA-29, September 2023.
24. Bahlis NJ, Quach H, Baz R, Vangsted A, Ho SJ, Abilgaard N, Laubach J, Ribrag V, Voorhees PM, Wang X, et al. Venetoclax in combination with daratumumab and dexamethasone elicits deep, durable responses in patients with t(11;14) relapsed/refractory multiple myeloma: updated analyses of minimal residual disease negativity in a phase 1 / 2 study. Blood 2023; 142(suppl.1): 338.
25. Szabo A, Thorsen J, Abilgaard N, Plesner T. Low-dose venetoclax-dexamethasone in t(11;14) positive relapsed and refractory multiple myeloma; interim results from the ongoing, Danish, investigator-initiated, open-label, phase 2 Victoria study. Blood 2023; 142 (suppl.1): 2020.
26. Leblay N, Ahn S, Tilmont R, Poorerbrahim M, Maity R, Lee H, Barakat E, Alberge JB, Sihna S, Jaffer A, et al. Integrated epigenetic and transcriptional single-cell analysis of t(11;14) multiple myeloma and its BCL2 dependency. Blood 2024; 143: 42-56.
27. Fonseca R, Oken MM, Greipp PR. The t(4 ;14)(p16.3 ;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance. Blood 2001; 98: 1271-1272.
28. Keats JJ, Reiman T, Maxwell CA, Taylor BJ, Lerratt LM, Mant MJ, Belch AW, Pilarski LM. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood 2003; 101: 1520-1529.
29. Binard B, Christofferson A, Legendre C, Aldrich J, Nassere S, Yesil J, Auclair D, Liang W, Lonial S, Keats JJ. FGFR3 mutations are an adverse prognostic factor in patients with t(4;14)(p16;p32) multiple myeloma: an Mmrf compass analysis. Blood 2017; 130(suppl.1): 3027.
30. Walker BA, Mavrommatis K, Wardell CP, Asbi TC, Bauer M, Davies FE, Rosenthal A, Wang H, Qu P, Hoering A, et al. Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 2018; 132: 587-597.
31. Walker BA, Wardell CP, Johnson DC. Characterization of IGH locus breakpoints indicates a subset of translocations appear to occur in pregerminal center B cells. Blood 2013; 121: 3413-3419.
32. Stong N, Ortiz-Estévez M, Towfic F, Samur M, Agarwal A, Corre J, Flynt E, Munshi N, Avet-Loiseau H, Thakurta A, et al. The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM. Blood 2023; 141: 1574-1583.
33. Geng C, Yang G, Zhou H, Wang H, Li Y, Leng Y, Zhang Z, Jian Y, Chen W. Prognostic value of t(4;14) translocation in newly diagnosed multiple myeloma patients in novel agent era. Hematology 2023; 28: 2161222.
34. Ozga M, Zhao Q, Huric L, Miller C, Rosko A, Khan A, Umyarova E, Benson D, Cottini F. Concomitant 1q+ and t(4;14) influences disease characteristics, immune system, and prognosis in double-hit multiple myeloma. Blood Cancer J 2023; 13: 167.
35. Schavgoulidze A, Perrot A, Cazaubiel T, Leleu X, Montes L, Jacquet C, Beladji K, Brechignac S, Frenzel L, Chalopin T, et al. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions. Blood Cancer J 2023; 13:160.
36. Cardona-Benavides JJ, Misiewicz-Krzeminska I, Rojas EA, De Ramon C, Sanz-Solas A, Isidro I, Quwaider D, Lopez-Guerrero AM, Cuadrado M, José-Calasanz M, et al. Quantification of cyclin D1 and D2 proteins in multiple myeloma identifies different expression patterns from those revealed by gene expression profiling. Haematologica 2023; in press.
37. Walker BA, Wardell CP, Murison A, Boyle EM, Begum DB, Dahir NM, Proszek PZ, Melchor L, Pawlyn C, Kaiser MF, et al. APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma. Nat Commun 2015; 6: 6997.
38. Papadimitriou M, Tauro M, Ziccheddu B, Poos AM, Alaoui YA, Meads MB, Maclachlan KH, Usmani SZ, Raab MS, Morgan GJ, et al. Genomic and transcriptomic landscape of hyper-Apobec multiple myeloma. Blood 2023; 142 (suppl.1): 639.
39. Schmidt TM, Barwick BG, Joseph N, Heffner LT, Hofmeister CC, Bernal L, Dhodapkar MV, Gupta VA, Jaye DL, Wu J, et al. Gain of chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone. Blood Cancer J 2019; 9: 94.
40. Grzasko N, Hus M, Pluta A, Jurcyszyn A, Walter-Croneck A, Morawska M, Chocholska S, Jajek R, Dmoszynska A. Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients. Hematol Oncol 2013; 31: 41-48.
41. Abdallah N, Greipp P, Kapoor P, Gertz MA, Dispenzieri A, Baughn LB, Lacy MO, Hayman SR, Buadi FK, Dingli D, et al. Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities. Blood Adv 2020; 4: 3509-3516.
42. D’Agostino M, Ruggeri M, Aquino S, Giuliani N, Arigoni M, Gentile M, Olivero M, Vincelli ID, Capra A, Mussatto C, et al. Impact of gain and amplification of 1q in newly diagnosed multiple myeloma patients receiving carfilzomib-based treatment in the Forte trial. Blood 2020; 138 (suppl.1): 1331.
43. Pasvolsky O, Ghanem S, Milton DR, Rauf M, Tanner MR, Bashir Q, Srour S, Saini N, Lin P, Ramdial J, et al. Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience. Blood Cancer J 2024; 14: 4.
44. Fonseca R, Arribas M, Ahmann G, Castro JC, Wiedmeier-Nutor EE, Baughn LB, Bergsagel PL, Fonseca R. Beyong the primary: unveiling the prognostic value of secondary cytogenetic abnormalities in multiple myeloma. Blood 2023; 142 (suppl.1): 2000.
45. Schmidt TM, Fonseca R, Usmani S. Chromosome 1q21 abnormalities in multiple myeloma. Blood Cancer J 2021; 11: 83.
46. Garcia JB, Eufemiese RA, Storti P, Sammnarelli G, Craviotto L, Todaro G, Toscani D, Marchica V, Giuliani N. Role of 1q21 in multiple myeloma: from pathogenesis to possible therapeutic targets. Cells 2021; 10: 1360.
47. Shaughnessy J, Tian E, Sawyer J, Bumm K, Landes R, Badros A, Morris C, Tricot G, Epstein J, Barlogie B. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96: 1505-1511.
48. Zojer N, Konigsberg R, Ackermann J, Fritz E, Dallinger S, Kromer E, Kaufmann H, Riedl L, Gisslinger H, Schreiber S, et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization. Blood 2000; 95: 1925-1930.
49. Walker BA, Boyle EM, Wardell CP, Murison A, Begum D, Dahir N, Proszek P, Johnson DC, Kaiser MF, Melchor L, Aronson LL, et al. Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma. J Clin Oncol 2015; 33: 3911-3920.
50. Binder M, Rajkumar SV, Ketterling RP, Greipp PT, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Hayman SR, Hwa YL, et al. Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma. Blood Cancer J 2017; 7: e600.
51. Chavan SS, He J, Tytarenko R, Deshpande S, Patel P, Bailey M, Stein CK, Stephens O, Weinhold N, Petty N, et al. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker. Blood Cancer J 2017; 7: e535.
52. Boyle EM, Ashby C, Tytarenko RG, Deshpande S, Wang H, Wang Y, Rosenthal A, Sawyer J, Tian E, Flynt E, et al. BRAF and DIS3 mutations associate with adverse outcome in a long-term follow-up of patients with multiple myeloma. Clin Cancer Res 2020; 26:2422-2432.
53. Todoert K, Ronchetti D, Favasuli V, Maura F, Morabito F, Bolli N, Taiana E, Neri A. DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome. Haematologica 2022; 107: 921-932.
54. Favasuli VK, Ronchetti D, Silvetsris I, Puccio N, Fabbiano G, Traini V, Todoerti K, Erratico S, Ciarrocchi A, et al. DIS3 depletion in multiple myeloma causes extensive perturbation in cell cycle progression and centrosome amplification. Haematologica 2024; 109: 231-240.
55. Kanasugi J, Hanamura I, Ota A, Karnan S, Lam YQ, Mizuno S, Wahiduzzaman M, Rahman ML, Hyodo T, Konishi H, et al. Biallelic loss of FAM46C triggers tumor growth with concomitant activation of Akt signaling in multiple myeloma cells. Cancer Sci 2020; 111: 1663-1675.
56. Zhu YX, Shi CX, Bruins LA, Jiedowski P, Wang X, Kortum HM, Luo M, Ahmann JM, Braggio E, Stewart AK. Loss of FAM46C promotes cell survival in myeloma. Cancer Res 2017; 77: 4317-4327.
57. Mroczek S, Chebowska J, Kulinski TM, Gewartoska O, Gruchota J, Cysekski D, Liudkovska V, Borsuk E, Nowis D, Dziemboski A. The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma. Nat Commun 2017; 8: 619.
58. Fucci C, Resnati M, Riva E, Perini T, Ruggieri E, Orfanelli U, Paradiso F, Cremasco F, Raimondi A, Pasqualetto E, et al. The interaction of the tumor suppressopr FAM46C with p62 and FNDC3 proteins integrates protein and secretory homeostasis. Cell Rep 2020; 32: 108162.
59. Resnati M, Pennacchio S, Viviani L, Perini T, Materozzi M, Orfanelli U, Bordini J, Molteni R, Nuvolone M, Da Vià M, et al. TENT/FAM46C modulation in vivo reveals a trade-off between antibody secretion and tumor growth in multiple myeloma. Haematologica 2024;109(6):1966-1972. doi: 10.3324/haematol.2023.284299.
60. Hofman IJF, van Duin M, De Bruyne E, Fancello L, Mulligan G, Geerdens E, Garelli E, Mancini C, Lemmens H, Delforge M, et al. RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response. Leukemia 2017; 31: 1706-1714.
61. Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, Dagrada G, Konn ZJ, Gregory WM, Jackson GH, et al. Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res 2011; 17: 7776-7784.
62. Hebraud B, Leleu X, Lauwers-Cances V, Roussel M, Caillot D, Marit G, Karlin L, Hulin C, Gentil C, Guilhot F, Garderet L, et al. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia 2014; 28: 675-679.
63. Shavgoulidze A, Talbot A, Perrot A, Cazaubiel T, Leleu X, Manier S, Buisson L, Mahéo S, Do Soto Ferreira L, Pavageau L, et al. Biallelic deletion of 1p32 defines ultra high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor. Blood 2023; 141: 1308-1315.
64. Vaishnav A, Khan A, Zhao Q, Bumma N, Cottini F, Umyarova E, Sharma N, Rosko AE, Benson D, Devarakonda S. Deletion 1p at time of diagnosis of multiple myeloma portends inferior outcomes. Blood 2023; 142( suppl.1): 1974.
65. Giri S, Huntigton SF, Wang R, Zeidan AM, Podoltsev N, Gore SD, Ma X, Gross CP, Davidoff AJ, Neparidze N. Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents. Blood Adv 2020; 4: 2245-2254.
66. Lodé L, Eveillard M, Trichet V, Soussi T, Waillème S, Richebourg S, Magrangeas F, Ifrah N, Campion L, Traullé C, et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma. Haematologica 2010; 95: 1973-1976.
67. Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, Rosenthal A, Wang H, Qu P, Hoering A, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia 2019; 33: 159-170.
68. Popek-Marciniec S, Styk W, Wojcierowska-Litwin M, Chocholska S, Szudy-Szczyrek A, Samardakiewicz M, Swiderska-Kolacz G, Czerwik-Marcinkowska J, Zmorzynski S. Association of Chromosome 17 Aneuploidy, TP53 Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment. Cancers (Basel). 2023 Sep 27;15(19):4747. doi: 10.3390/cancers15194747.
69. Chin M, Sive JI, Allen C, Roddie C, Chavda SJ, Smith D, Blombery P, Jones K, Ryland GL, Popat R, et al. Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on survival. Blood Cancer J 2017; 7: e610.
70. Corre J, Perrot A, Caillot D, Belhadj K, Hulin C, Leleu X, Mothy M, Facon T, Buisson L, Do Souto L, et al. del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma. Blood 2021; 137: 1192-1195.
71. Liu E, Sudha P, Becker N, Jaouadi O, Sauvannasankha A, Lee K, Abonour R, Zaid MA, Walker BA. Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma. Blood Cancer J 2023; 13: 44.
72. Lakshman A, Painuly U, Rajkumar SV, Ketterling RP, Kapoor P, Greipp PT, Dispenzieri A, Gertz MA, Buadi FK, Dingli D, et al. Impact of acquired del(17p) in multiple myeloma. Blood Adv 2019; 3: 1930-1938.
73. An G, Li Z, Tai YT Acharya C, Li Q, Qiu X, Yi S, Xu Y, Feng X, Li C, et al. The impact of clone size on the prognostic value of chromosome aberrations by fluorescence in situ hybridization in multiple myeloma. Clin Cancer Res 2015; 21: 2148-2156.
74. Thanendrarajan S, Tian E, Qu P, Mathur P, Schinke C, van Rhee F, Zangari M, Rasche L, Weinhold N, Arlapat D, et al. The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma. Haematologica 2017; 102: e364-e367.
75. Martello M, Poletti A, Borsi E, Solli V, Dozza L, Barbato S, Zamagni E, Tacchetti P, Pantani L, Mancuso K, Vigliotta I, Rizzello I, Rocchi S, Armuzzi S, Testoni N, Marzocchi G, Martinelli G, Cavo M, Terragna C. Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma. Blood Cancer J. 2022 Jan 26;12(1):15. Thakurta A, Ortiz M, Blecua P, Towfic F, Corre J, Serbina NV, Flynt E, Yu Z, Yang Z, Palumbo A, et al. High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma. Blood 2019; 133: 1217-1221.
76. Cui JC, Lv R, Yu T, Yan W, Xu J, Fan H, Li L, Liu Y, Du C, Deng S, et al. Minor clone of del(17p) provides a reservoir for relapse in multiple myeloma. Haematologica 2024; 109: 591-603.
77. Jurgens E, Firestone R, Maclachlan KH, Nemirosky D, Derkach A, Hultcrantz M, Hassoun H, Mailankody S, Shah UA, Rajeeve. Clinical outcomes associated with del(17p) in newly diagnosed multiple myeloma treated with triplet and duratumumab-based quadruplet induction regiman. Blood 2023; 142(suppl.1): page 2024.
78. Mohan M, Gong Z, Ashby TC, Al Hadidi S, Thanendrarajan S, Schinke C, Alapat D, Shaughnessy JD, Zhan F, van Rhee F, et al. Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma. Cancer 2023; 129: 2491-2498.
79. Chng WJ, Huang GF, Chung TH, Ng SS, Gonzalez-Paz N, Troska-Price T, Mulligan G, Chesi M, Bergsagel PL, Fonseca R. Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnoses multiple myeloma. Leukemia 2011; 25: 1026-1035.
80. Affer M, Chesi M, Chen WG, Keats JJ, Demchenko YN, Roshke AV. Promiscuous MYC locus rearrangements hijack enhancers but mostly superenhancers to dysregulate MYC expression in multiple myeloma. Leukemia 2014; 28: 1725-1735.
81. Walker BA, Wardell CP, Brioli A, Boyle E, Kaiser MF, Begum DB. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients. Blood Cancer J 2014; 4: e191.
82. Jovanović KK, Roche-Lestienne C, Ghobrial IM, Facon T, Quesnel B, Manier S. Targeting MYC in multiple myeloma. Leukemia. 2018 Jun;32(6):1295-1306. doi: 10.1038/s41375-018-0036-x.
83. Misund K, Keane N, Stein CK, Asmann YW, Day G, Welsh S, Wier SV, Riggs D, Ahmann G, Chesi M, et al. MYC deregulation in the progression of multiple myeloma. Leukemia 2020; 34: 322-326.
84. Abdallah N, Baughn LB, Rajkumar SV, Kapoor P, Gertz MA, Dispenzieri A, Lacy MQ. Hayman SR, Buadi FK, Dingli D, et al. Implications of MYC rearrangements in newly diagnosed multiple myeloma. Clin Cancer Res 2020; 26: 6581-6588.
85. Smadbeck J, Peterson JF, Pearce KE, Pitel BA, Figueroa AL, Timm M, Jevremovic D, Shi M, Stewart AK, Braggio E, et al. Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma. Blood Cancer J 2019; 9: 103.
86. Sharma N, Smadbeck J, Adballah N, Zepada-Mendoza C, Binder M, Pearce KE, Asmann YW, Peterson JF, Ketterling RP, Greipp PT, et al. The prognostic role of MYC structural variants identified by NGS and FISH in multiple myeloma. Clin Cancer Res 2021; 27: 5430-5439.
87. Barwick BG, Neri P, Bahlis NJ, Nooka AK, Dhodapkar MV, Jaye DL, Hofmeister CC, Kaufman JL, Gupta VA, Auclair D, et al. Multiple myeloma immunoglobulin lambda translocations portend poor prognosis. Nat Commun 2019; 10: 1911.
88. Clarke SE, Fuller KA, Erber WN. Chromosomal defects in multiple myeloma. Blood Rev. 2024 Mar;64:101168. doi: 10.1016/j.blre.2024.101168.
89. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, et al. Initial genome sequencing and analysis of multiple myeloma Nature 2011; 471: 467-474.
90. Bolli N, Biancon G, Moarii M, Gimondi S, Li Y, de Philippis C, Maura F, Sathiaseelan V, Tai YT, Mudle L, et al. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia 2018; 32: 2604-2616.
91. Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, Tytarenko R, Buaer MA, Meissner T, Deshpande S, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood 2016; 128: 1735-1744.
92. Ziccheddu B, Biancon G, Bagnoli F, De Philippis C, Maura F, Rustad EH, Dugo M, Devecchi A, De Cecco L, Sensi M, et al. Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma. Blood Advances 2020; 4: 830-840
93. Vo JN, Wu YM, Mishler JM, Hall S, Mannan R, Wang L, Ning Y, Zhou J, Hopkins AC, Estill JC, et al. The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma. Nat Commun 2022; 13: 3750.
94. Kortum KM, Mai EK, Hanafiah NH, Shi CX, Zu YX, Bruins L, Barrio S, Jedlowski P, Merz M, Hu J, et al. Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes. Blood 2016; 128: 1226-1233.
95. Gooding S, Ansari-Pour N, Towfic F, Estevez MO, Chamberlain PP, Fsai KT, Flynt E, Rozelle D, Dhiman P, Neri P, et al. Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood 2021; 137: 232-237.
96. Zhu YX, Ahmann GJ, Bruins A, Arribas M, Chen X, Chesi M, Bergsagel PL, Fonseca R, Rimaza LM. Newly, diagnosed, untreated, multiple myeloma (MM) patient samples already harbor cereblon (CRBN) exon 10 deletions associated with drug resistance. Blood 2022; 140 (suppl.1): 4187-4188.
97. Giesien N, Paramasivam N, Toprak UK, Huebschmann D, Xu J, Uhrig S, Samur M, Bahr S,Frolich M, Mughal SS, et al. Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities. Haematologica 2022; 107: 1891-1901.
98. Ansari-Pour N, Samur M, Flynt E, Gooding S, Towfic F, Stong N, Estevez MO, Mavrommatis K, Walker B, Morgan G, et al. Whole-genome analysis identifies novel drivers and high-risk double-hit events in relapsed/refractory myeloma. Blood 2023; 141: 620-633.
99. Braunstein M, Blaney P, Morgan GJ. Whole-genome sequencing identifies structural variation as a key driver of disease relapse and aggressive clinical behavior in multiple myeloma. Blood 2023; 142 (suppl.1): 2773. Braunstein M, Blaney P, Morgan GJ. Whole-genome sequencing identifies structural variation as a key driver of disease relapse and aggressive clinical behavior in multiple myeloma. Blood 2023; 142 (suppl.1): 2773.
100. Rustad EH, Yellapantula VD, Glodzik D, Maclachlan KH, Diamond B, Boyle EM, Ashby C, Blaney P, Gundem G, Hultcrantz M, et al. Revealing the impact of structural variants in multiple myeloma. Blood Cancer Discov 2020; 1: 258-273.
101. Maclachlan KH, Rustad EH, Derkach A, Zheng-Li B, Yellapantula V, Diamond B, Hultcrantz M, Ziccheddu B, Boyle EM, Blaney P, et al. Copy number signatures predict chromotripsis and clinical outcomes in newly diagnosed multiple myeloma. Nat Commun 2021; 12: 5172.
102. Yu J, Chen N, Zheng Z, Gao M, Liang N, Wang KC. Chromotripsis detection with multiple myeloma patients based on deep graph learning. Bioinformatics 2023; 39: btads422.
103. Maclachlan KH, Ziccheddu B, Tan C, Shekarkhand T, Rueda C, Serrano E, Diamond B, Hassoun H, Mailankody S, Shah UA, et al. The complex structural variant chromotripsis can be defined on targeted sequencing panels, allowing direct clinical transition in order to improve multiple myeloma prognostication. Blood 2023; 142: 3343.
104. Maura F, Boyle EM, Rustad EH, Ashby C, Kaminetzky D, Bruno B, Braunstein M, Bauer M, Blaney P, Wang Y, Ghamalouch H, et al. Chromotripsis as a pathogenic driver of multiple myeloma. Semin Cell Dev Biol 2022; 123: 115-123.
105. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardon P, Caltagirone S, Lahuerta JJ, Facon T, et al. Revised international staging system for multiple myeloma: a report from the international myeloma working group. J Clin Oncol 2015; 33: 2863-2869.
106. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 2022; 97: 1086-1107.
107. Weinhold N, Salwender HJ, Cairn DA, Raab MS, Waldron G, Balu LW, Bertsch U, Hielscher T, Morgan GJ, Janch A, et al. Chromosome 1p21 abnormalities refine outcome prediction in patients with multiple myeloma-a meta-analysis of 2,596 patients. Haematologica 2021; 106: 2754-2758.
108. Schavgoulidze A, Lauwers-Cances V, Perrot A, Cazaubiel T, Chretien ML, Moreau P, Facon T, Leleu X, Karlin L, Stoppa AM, et al. Heterogeneity in long-term outcomes for patients with revised international staging system stage II, newly diagnosed multiple myeloma. Haematologica 2023; 108: 1374-1384.
109. D’Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall’Olio D, van de Donk D, et al. Second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma: a European myeloma network (EMN) report within the HARMONY project. J Clin Oncol 2022; 40: 3406-3418.
110. Perrot A, Lauwers-Cances V, Tournay E, Hulin C, Chretien ML, Royer B, Dib M, Decaux O, Jaccard A, Belhadij K, et al. Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol 2019; 37: 1657-1665.
111. Alzahrani K, Paslovsky O, Wang Z, Milton DR, Tanner MR, Bashir Q, Srour SA, Saini NY, Lin P, Ramdial J, et al. Impact of revised international staging system 2 (R2-ISS) risk stratification on outcomes of patients with multiple myeloma receiving autologous hematopoietic stem cell transplantation. Blood 2023; 142 (suppl. 1): 3356.
112. Guo W, Zhan A, Mary DE, Munshi MN, Makhoul O, Bally C, Zangari M, Tricot G, Peng H, Shaghnessy JD. Application of R2-ISS risk stratification to patients with multiple myeloma treated with autologous stem cell transplants at UAMS. Blood Adv 2023; 7: 6676-6684.
113. Panopoulou A, Easdale S, Ethell M, Nihcolson E, Potter M, Giotas E, Woods H, Thornton T, Pawlyn C, Boyd KD, et al. Impact of ultra high-risk genetics on real-world outcomes of transplant-eligible multiple myeloma patients. HemaSphere 2023; 7: e831.
114. Panopoulou A, Cairns DA, Holroyd A, Nichols I, Nichols I, Cray N, Pawlkyn C, Cook G, Drayson M, Boyd K, et al. Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial. Blood 2023; 141: 1666-1674.
115. Pham P, Sudha P, Wang L, Niu W, Morgan C, Ligocki C, Al-Azzawi R, Ly R, Vetrini F, Czader M, et al. Prospective molecular characterization of multiple myeloma patient samples identifies high-risk patients and informs treatment sequences through resistance mechanisms to immunotherapies. Blood 2023; 142(suppl.1): 4738.
116. Andreozzi F, Dragani M, Quivoron C, Le Bras F, Assi T, Danu A, Belhadj K, Lazarovici J, Cotteret S, Bernard OA, Ribrag V, Michot JM. Precision Medicine Approach Based on Molecular Alterations for Patients with Relapsed or Refractory Multiple Myeloma: Results from the MM-EP1 Study. Cancers (Basel). 2023 Feb 28;15(5):1508. doi: 10.3390/cancers15051508samples
2. Rajkumar SV, Landgren O, Mateos MV. Smouldering multiple myeloma. Blood 2015; 125: 3069-3075.
3. Walker BA, Leone PE. Chiecchio L, Dickens NJ, Jenner MW, Boyd KD, Johnson DC, Gonzalez D, Dagrada GP, Protheroa R, et al. A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood 2010; 116: e56-65.
4. Barwick BG, Gupta VA, Verino PM, Boise LH. Cell of origin and genetic alterations in the pathogenesis of multiple myeloma. Front Immunol 2019; 10: 1121.
5. Samur AA, Minelli S, Shammas M, Falciniti M, Magrangeas F, Richardson PG, Moreau P, Attal M, Anderson KC, Parmigiani G, et al. Deciphering the chronology of copy number alterations in multiple myeloma. Blood Cancer 2019; 9: 39.
6. Maura F, Bolli N, Angelopoulos N, Dawson KJ, Leogmornlert D, Martincorena I, Mitchell TJ, Fullam A, Gonzalez S, Szalat R, et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun 2019; 10: 3835.
7. Shah V, Sherborne AL, Walker BA, Johnson DC, Boyle EM, Ellis S, Begum DB, Proszek PZ, Jones JR, Pawlyn C, et al. Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles in 1905 trial patients. Leukemia 2018; 32:102-110.
8. Barilà G, Bonaldi L, Grassi A, Martines A, Lico A, Macrì N, Nalio S, Pavan L, Berno T, Branca A, et al. Identification of the true hyperdiploid multiple myeloma subset by combining conventional karyotyping and FISH analysis. Blood Cancer J 2020; 10: 18.
9. Wang Y, Zhuang J, An G, Mao XH, Du C, Liu J, Fan H, Deng S, Xu Y, Sui W, et al. Prognostic impact of hyperploidy on multiple myeloma in the era of new agents. Blood 2020; 136(suppl.1): 20.
10. Samur MK, Samur AA, Fulciniti MT, Szalat R, Han T, Shammas M, Richardson P, Magrangeas F, Minvielle S, Corre J, et al. Genome-wide somatic alterations in multiple myeloma reveal a superior outcome group. J Clin Oncol 2020; 38: 3107-3118.
11. Pawlyn C, Melchor L, Murison A, Wardell CP, Brioli A, Boyle EM, Kaiser MF, Walker BA, Begum DB, Dahir NB, Proszek P, et al. Coexistent hyperploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH translocations. Blood 2015; 125: 831-840.
12. Wiedmeier-Nutor_JE, Bergsagel PL. Review of multiple myeloma genetics including effects on prognosis, response to treatment, and diagnostic workup. Life 2022; 22: 812.
13. Hanamura I, Iida S, Ueda R, Kuehl M, Cullraro C, Bergsagel L, Sawyer J, Barlogie B, Shaughnessy J. Identification of three novel chromosomal translocation partners involving the immunoglobulin loci in newly diagnosed myeloma and human myeloma cell lines. Blood 2005 ; 106 : 1552.
14. Hanamura I. Multiple myeloma with high-risk cytogenetics and its treatment approach. Int J Haematol 2022 ; 115 : 762-777.
15. Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J. Cyclin D regulation: an early and unifying pathogenic event in multiple myeloma. Blood 2005; 106: 296-303.
16. Bal S, Kumar SK, Fonseca R, Gay F, Hungria V, Dogan A, Costa LJ. Multiple myeloma with t(11;14): unique biology and evolving landscape. Am J Cancer Res 2022; 12: 2950-2965.
17. Ross JA, Avet-Loiseau H, Li X, Thiebaut-Millot R, Hader C. Genomic landscape of t(11;14) in multiple myeloma. Blood 2022; 140(suppl.1): 10092-10093.
18. Avet-Loiseau H, Thiébaut-Millot R, Li X, Ross JA, Hader C. t(11;14) status is stable between diagnosis and relapse, and concordant between detection methodologies based on fluorescence in situ hybridization and next-generation sequencing in patients with multiple myeloma. Haematologica 2024; in press.
19. Maura F, Rajanna AR, Ziccheddu B, Poos AM, Derkach A, Maclachlan K, Durante M, Diamond B, Papadimitriou M, Davies F, et al. Genomic classification and individualized prognosis in multiple myeloma. J Clin Oncol 2024; 42: 1229-1240.
20. Ziccheddu B, Da Vià MC, Lionetti M, Maeda A, Morlupi S, Dugo M, Todoerti K, Olivia S, D’Agostino M, Corradini P, et al. Functional impact of genomic complexity on the transcriptome of multiple myeloma. Clin Cancer Res 2021; 27: 6479-6490.
21. Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, Hungria V, Salwender H, Suzuki K, Kim I, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomized, double-blind, multicentre, phase 3 trial. Lancet Oncol 2020; 21: 1630-1642.
22. Mateos MV, Beksac M, Dismopoulos MA, et al. Results from the randomized, open-label phase 3 CANOVA study of venetoclax-dexamethasone versus pomalidomide-dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma. International Myeloma Society 2023 Annual Meeting. Abstract OA-25, September 2023.
23. Kaufman JL, Gasparetto C, Kovacsovics T, et al. Frist results from the randomized portion of a phase 2 study of venetoclax plus carfilzomib-dexamethasone vs carfilzomib-dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma. International Myeloma Society 2023 Annual Meeting. Abstract OA-29, September 2023.
24. Bahlis NJ, Quach H, Baz R, Vangsted A, Ho SJ, Abilgaard N, Laubach J, Ribrag V, Voorhees PM, Wang X, et al. Venetoclax in combination with daratumumab and dexamethasone elicits deep, durable responses in patients with t(11;14) relapsed/refractory multiple myeloma: updated analyses of minimal residual disease negativity in a phase 1 / 2 study. Blood 2023; 142(suppl.1): 338.
25. Szabo A, Thorsen J, Abilgaard N, Plesner T. Low-dose venetoclax-dexamethasone in t(11;14) positive relapsed and refractory multiple myeloma; interim results from the ongoing, Danish, investigator-initiated, open-label, phase 2 Victoria study. Blood 2023; 142 (suppl.1): 2020.
26. Leblay N, Ahn S, Tilmont R, Poorerbrahim M, Maity R, Lee H, Barakat E, Alberge JB, Sihna S, Jaffer A, et al. Integrated epigenetic and transcriptional single-cell analysis of t(11;14) multiple myeloma and its BCL2 dependency. Blood 2024; 143: 42-56.
27. Fonseca R, Oken MM, Greipp PR. The t(4 ;14)(p16.3 ;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance. Blood 2001; 98: 1271-1272.
28. Keats JJ, Reiman T, Maxwell CA, Taylor BJ, Lerratt LM, Mant MJ, Belch AW, Pilarski LM. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood 2003; 101: 1520-1529.
29. Binard B, Christofferson A, Legendre C, Aldrich J, Nassere S, Yesil J, Auclair D, Liang W, Lonial S, Keats JJ. FGFR3 mutations are an adverse prognostic factor in patients with t(4;14)(p16;p32) multiple myeloma: an Mmrf compass analysis. Blood 2017; 130(suppl.1): 3027.
30. Walker BA, Mavrommatis K, Wardell CP, Asbi TC, Bauer M, Davies FE, Rosenthal A, Wang H, Qu P, Hoering A, et al. Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 2018; 132: 587-597.
31. Walker BA, Wardell CP, Johnson DC. Characterization of IGH locus breakpoints indicates a subset of translocations appear to occur in pregerminal center B cells. Blood 2013; 121: 3413-3419.
32. Stong N, Ortiz-Estévez M, Towfic F, Samur M, Agarwal A, Corre J, Flynt E, Munshi N, Avet-Loiseau H, Thakurta A, et al. The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM. Blood 2023; 141: 1574-1583.
33. Geng C, Yang G, Zhou H, Wang H, Li Y, Leng Y, Zhang Z, Jian Y, Chen W. Prognostic value of t(4;14) translocation in newly diagnosed multiple myeloma patients in novel agent era. Hematology 2023; 28: 2161222.
34. Ozga M, Zhao Q, Huric L, Miller C, Rosko A, Khan A, Umyarova E, Benson D, Cottini F. Concomitant 1q+ and t(4;14) influences disease characteristics, immune system, and prognosis in double-hit multiple myeloma. Blood Cancer J 2023; 13: 167.
35. Schavgoulidze A, Perrot A, Cazaubiel T, Leleu X, Montes L, Jacquet C, Beladji K, Brechignac S, Frenzel L, Chalopin T, et al. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions. Blood Cancer J 2023; 13:160.
36. Cardona-Benavides JJ, Misiewicz-Krzeminska I, Rojas EA, De Ramon C, Sanz-Solas A, Isidro I, Quwaider D, Lopez-Guerrero AM, Cuadrado M, José-Calasanz M, et al. Quantification of cyclin D1 and D2 proteins in multiple myeloma identifies different expression patterns from those revealed by gene expression profiling. Haematologica 2023; in press.
37. Walker BA, Wardell CP, Murison A, Boyle EM, Begum DB, Dahir NM, Proszek PZ, Melchor L, Pawlyn C, Kaiser MF, et al. APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma. Nat Commun 2015; 6: 6997.
38. Papadimitriou M, Tauro M, Ziccheddu B, Poos AM, Alaoui YA, Meads MB, Maclachlan KH, Usmani SZ, Raab MS, Morgan GJ, et al. Genomic and transcriptomic landscape of hyper-Apobec multiple myeloma. Blood 2023; 142 (suppl.1): 639.
39. Schmidt TM, Barwick BG, Joseph N, Heffner LT, Hofmeister CC, Bernal L, Dhodapkar MV, Gupta VA, Jaye DL, Wu J, et al. Gain of chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone. Blood Cancer J 2019; 9: 94.
40. Grzasko N, Hus M, Pluta A, Jurcyszyn A, Walter-Croneck A, Morawska M, Chocholska S, Jajek R, Dmoszynska A. Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients. Hematol Oncol 2013; 31: 41-48.
41. Abdallah N, Greipp P, Kapoor P, Gertz MA, Dispenzieri A, Baughn LB, Lacy MO, Hayman SR, Buadi FK, Dingli D, et al. Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities. Blood Adv 2020; 4: 3509-3516.
42. D’Agostino M, Ruggeri M, Aquino S, Giuliani N, Arigoni M, Gentile M, Olivero M, Vincelli ID, Capra A, Mussatto C, et al. Impact of gain and amplification of 1q in newly diagnosed multiple myeloma patients receiving carfilzomib-based treatment in the Forte trial. Blood 2020; 138 (suppl.1): 1331.
43. Pasvolsky O, Ghanem S, Milton DR, Rauf M, Tanner MR, Bashir Q, Srour S, Saini N, Lin P, Ramdial J, et al. Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience. Blood Cancer J 2024; 14: 4.
44. Fonseca R, Arribas M, Ahmann G, Castro JC, Wiedmeier-Nutor EE, Baughn LB, Bergsagel PL, Fonseca R. Beyong the primary: unveiling the prognostic value of secondary cytogenetic abnormalities in multiple myeloma. Blood 2023; 142 (suppl.1): 2000.
45. Schmidt TM, Fonseca R, Usmani S. Chromosome 1q21 abnormalities in multiple myeloma. Blood Cancer J 2021; 11: 83.
46. Garcia JB, Eufemiese RA, Storti P, Sammnarelli G, Craviotto L, Todaro G, Toscani D, Marchica V, Giuliani N. Role of 1q21 in multiple myeloma: from pathogenesis to possible therapeutic targets. Cells 2021; 10: 1360.
47. Shaughnessy J, Tian E, Sawyer J, Bumm K, Landes R, Badros A, Morris C, Tricot G, Epstein J, Barlogie B. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96: 1505-1511.
48. Zojer N, Konigsberg R, Ackermann J, Fritz E, Dallinger S, Kromer E, Kaufmann H, Riedl L, Gisslinger H, Schreiber S, et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization. Blood 2000; 95: 1925-1930.
49. Walker BA, Boyle EM, Wardell CP, Murison A, Begum D, Dahir N, Proszek P, Johnson DC, Kaiser MF, Melchor L, Aronson LL, et al. Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma. J Clin Oncol 2015; 33: 3911-3920.
50. Binder M, Rajkumar SV, Ketterling RP, Greipp PT, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Hayman SR, Hwa YL, et al. Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma. Blood Cancer J 2017; 7: e600.
51. Chavan SS, He J, Tytarenko R, Deshpande S, Patel P, Bailey M, Stein CK, Stephens O, Weinhold N, Petty N, et al. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker. Blood Cancer J 2017; 7: e535.
52. Boyle EM, Ashby C, Tytarenko RG, Deshpande S, Wang H, Wang Y, Rosenthal A, Sawyer J, Tian E, Flynt E, et al. BRAF and DIS3 mutations associate with adverse outcome in a long-term follow-up of patients with multiple myeloma. Clin Cancer Res 2020; 26:2422-2432.
53. Todoert K, Ronchetti D, Favasuli V, Maura F, Morabito F, Bolli N, Taiana E, Neri A. DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome. Haematologica 2022; 107: 921-932.
54. Favasuli VK, Ronchetti D, Silvetsris I, Puccio N, Fabbiano G, Traini V, Todoerti K, Erratico S, Ciarrocchi A, et al. DIS3 depletion in multiple myeloma causes extensive perturbation in cell cycle progression and centrosome amplification. Haematologica 2024; 109: 231-240.
55. Kanasugi J, Hanamura I, Ota A, Karnan S, Lam YQ, Mizuno S, Wahiduzzaman M, Rahman ML, Hyodo T, Konishi H, et al. Biallelic loss of FAM46C triggers tumor growth with concomitant activation of Akt signaling in multiple myeloma cells. Cancer Sci 2020; 111: 1663-1675.
56. Zhu YX, Shi CX, Bruins LA, Jiedowski P, Wang X, Kortum HM, Luo M, Ahmann JM, Braggio E, Stewart AK. Loss of FAM46C promotes cell survival in myeloma. Cancer Res 2017; 77: 4317-4327.
57. Mroczek S, Chebowska J, Kulinski TM, Gewartoska O, Gruchota J, Cysekski D, Liudkovska V, Borsuk E, Nowis D, Dziemboski A. The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma. Nat Commun 2017; 8: 619.
58. Fucci C, Resnati M, Riva E, Perini T, Ruggieri E, Orfanelli U, Paradiso F, Cremasco F, Raimondi A, Pasqualetto E, et al. The interaction of the tumor suppressopr FAM46C with p62 and FNDC3 proteins integrates protein and secretory homeostasis. Cell Rep 2020; 32: 108162.
59. Resnati M, Pennacchio S, Viviani L, Perini T, Materozzi M, Orfanelli U, Bordini J, Molteni R, Nuvolone M, Da Vià M, et al. TENT/FAM46C modulation in vivo reveals a trade-off between antibody secretion and tumor growth in multiple myeloma. Haematologica 2024;109(6):1966-1972. doi: 10.3324/haematol.2023.284299.
60. Hofman IJF, van Duin M, De Bruyne E, Fancello L, Mulligan G, Geerdens E, Garelli E, Mancini C, Lemmens H, Delforge M, et al. RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response. Leukemia 2017; 31: 1706-1714.
61. Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, Dagrada G, Konn ZJ, Gregory WM, Jackson GH, et al. Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res 2011; 17: 7776-7784.
62. Hebraud B, Leleu X, Lauwers-Cances V, Roussel M, Caillot D, Marit G, Karlin L, Hulin C, Gentil C, Guilhot F, Garderet L, et al. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia 2014; 28: 675-679.
63. Shavgoulidze A, Talbot A, Perrot A, Cazaubiel T, Leleu X, Manier S, Buisson L, Mahéo S, Do Soto Ferreira L, Pavageau L, et al. Biallelic deletion of 1p32 defines ultra high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor. Blood 2023; 141: 1308-1315.
64. Vaishnav A, Khan A, Zhao Q, Bumma N, Cottini F, Umyarova E, Sharma N, Rosko AE, Benson D, Devarakonda S. Deletion 1p at time of diagnosis of multiple myeloma portends inferior outcomes. Blood 2023; 142( suppl.1): 1974.
65. Giri S, Huntigton SF, Wang R, Zeidan AM, Podoltsev N, Gore SD, Ma X, Gross CP, Davidoff AJ, Neparidze N. Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents. Blood Adv 2020; 4: 2245-2254.
66. Lodé L, Eveillard M, Trichet V, Soussi T, Waillème S, Richebourg S, Magrangeas F, Ifrah N, Campion L, Traullé C, et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma. Haematologica 2010; 95: 1973-1976.
67. Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, Rosenthal A, Wang H, Qu P, Hoering A, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia 2019; 33: 159-170.
68. Popek-Marciniec S, Styk W, Wojcierowska-Litwin M, Chocholska S, Szudy-Szczyrek A, Samardakiewicz M, Swiderska-Kolacz G, Czerwik-Marcinkowska J, Zmorzynski S. Association of Chromosome 17 Aneuploidy, TP53 Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment. Cancers (Basel). 2023 Sep 27;15(19):4747. doi: 10.3390/cancers15194747.
69. Chin M, Sive JI, Allen C, Roddie C, Chavda SJ, Smith D, Blombery P, Jones K, Ryland GL, Popat R, et al. Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on survival. Blood Cancer J 2017; 7: e610.
70. Corre J, Perrot A, Caillot D, Belhadj K, Hulin C, Leleu X, Mothy M, Facon T, Buisson L, Do Souto L, et al. del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma. Blood 2021; 137: 1192-1195.
71. Liu E, Sudha P, Becker N, Jaouadi O, Sauvannasankha A, Lee K, Abonour R, Zaid MA, Walker BA. Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma. Blood Cancer J 2023; 13: 44.
72. Lakshman A, Painuly U, Rajkumar SV, Ketterling RP, Kapoor P, Greipp PT, Dispenzieri A, Gertz MA, Buadi FK, Dingli D, et al. Impact of acquired del(17p) in multiple myeloma. Blood Adv 2019; 3: 1930-1938.
73. An G, Li Z, Tai YT Acharya C, Li Q, Qiu X, Yi S, Xu Y, Feng X, Li C, et al. The impact of clone size on the prognostic value of chromosome aberrations by fluorescence in situ hybridization in multiple myeloma. Clin Cancer Res 2015; 21: 2148-2156.
74. Thanendrarajan S, Tian E, Qu P, Mathur P, Schinke C, van Rhee F, Zangari M, Rasche L, Weinhold N, Arlapat D, et al. The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma. Haematologica 2017; 102: e364-e367.
75. Martello M, Poletti A, Borsi E, Solli V, Dozza L, Barbato S, Zamagni E, Tacchetti P, Pantani L, Mancuso K, Vigliotta I, Rizzello I, Rocchi S, Armuzzi S, Testoni N, Marzocchi G, Martinelli G, Cavo M, Terragna C. Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma. Blood Cancer J. 2022 Jan 26;12(1):15. Thakurta A, Ortiz M, Blecua P, Towfic F, Corre J, Serbina NV, Flynt E, Yu Z, Yang Z, Palumbo A, et al. High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma. Blood 2019; 133: 1217-1221.
76. Cui JC, Lv R, Yu T, Yan W, Xu J, Fan H, Li L, Liu Y, Du C, Deng S, et al. Minor clone of del(17p) provides a reservoir for relapse in multiple myeloma. Haematologica 2024; 109: 591-603.
77. Jurgens E, Firestone R, Maclachlan KH, Nemirosky D, Derkach A, Hultcrantz M, Hassoun H, Mailankody S, Shah UA, Rajeeve. Clinical outcomes associated with del(17p) in newly diagnosed multiple myeloma treated with triplet and duratumumab-based quadruplet induction regiman. Blood 2023; 142(suppl.1): page 2024.
78. Mohan M, Gong Z, Ashby TC, Al Hadidi S, Thanendrarajan S, Schinke C, Alapat D, Shaughnessy JD, Zhan F, van Rhee F, et al. Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma. Cancer 2023; 129: 2491-2498.
79. Chng WJ, Huang GF, Chung TH, Ng SS, Gonzalez-Paz N, Troska-Price T, Mulligan G, Chesi M, Bergsagel PL, Fonseca R. Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnoses multiple myeloma. Leukemia 2011; 25: 1026-1035.
80. Affer M, Chesi M, Chen WG, Keats JJ, Demchenko YN, Roshke AV. Promiscuous MYC locus rearrangements hijack enhancers but mostly superenhancers to dysregulate MYC expression in multiple myeloma. Leukemia 2014; 28: 1725-1735.
81. Walker BA, Wardell CP, Brioli A, Boyle E, Kaiser MF, Begum DB. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients. Blood Cancer J 2014; 4: e191.
82. Jovanović KK, Roche-Lestienne C, Ghobrial IM, Facon T, Quesnel B, Manier S. Targeting MYC in multiple myeloma. Leukemia. 2018 Jun;32(6):1295-1306. doi: 10.1038/s41375-018-0036-x.
83. Misund K, Keane N, Stein CK, Asmann YW, Day G, Welsh S, Wier SV, Riggs D, Ahmann G, Chesi M, et al. MYC deregulation in the progression of multiple myeloma. Leukemia 2020; 34: 322-326.
84. Abdallah N, Baughn LB, Rajkumar SV, Kapoor P, Gertz MA, Dispenzieri A, Lacy MQ. Hayman SR, Buadi FK, Dingli D, et al. Implications of MYC rearrangements in newly diagnosed multiple myeloma. Clin Cancer Res 2020; 26: 6581-6588.
85. Smadbeck J, Peterson JF, Pearce KE, Pitel BA, Figueroa AL, Timm M, Jevremovic D, Shi M, Stewart AK, Braggio E, et al. Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma. Blood Cancer J 2019; 9: 103.
86. Sharma N, Smadbeck J, Adballah N, Zepada-Mendoza C, Binder M, Pearce KE, Asmann YW, Peterson JF, Ketterling RP, Greipp PT, et al. The prognostic role of MYC structural variants identified by NGS and FISH in multiple myeloma. Clin Cancer Res 2021; 27: 5430-5439.
87. Barwick BG, Neri P, Bahlis NJ, Nooka AK, Dhodapkar MV, Jaye DL, Hofmeister CC, Kaufman JL, Gupta VA, Auclair D, et al. Multiple myeloma immunoglobulin lambda translocations portend poor prognosis. Nat Commun 2019; 10: 1911.
88. Clarke SE, Fuller KA, Erber WN. Chromosomal defects in multiple myeloma. Blood Rev. 2024 Mar;64:101168. doi: 10.1016/j.blre.2024.101168.
89. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, et al. Initial genome sequencing and analysis of multiple myeloma Nature 2011; 471: 467-474.
90. Bolli N, Biancon G, Moarii M, Gimondi S, Li Y, de Philippis C, Maura F, Sathiaseelan V, Tai YT, Mudle L, et al. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia 2018; 32: 2604-2616.
91. Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, Tytarenko R, Buaer MA, Meissner T, Deshpande S, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood 2016; 128: 1735-1744.
92. Ziccheddu B, Biancon G, Bagnoli F, De Philippis C, Maura F, Rustad EH, Dugo M, Devecchi A, De Cecco L, Sensi M, et al. Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma. Blood Advances 2020; 4: 830-840
93. Vo JN, Wu YM, Mishler JM, Hall S, Mannan R, Wang L, Ning Y, Zhou J, Hopkins AC, Estill JC, et al. The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma. Nat Commun 2022; 13: 3750.
94. Kortum KM, Mai EK, Hanafiah NH, Shi CX, Zu YX, Bruins L, Barrio S, Jedlowski P, Merz M, Hu J, et al. Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes. Blood 2016; 128: 1226-1233.
95. Gooding S, Ansari-Pour N, Towfic F, Estevez MO, Chamberlain PP, Fsai KT, Flynt E, Rozelle D, Dhiman P, Neri P, et al. Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood 2021; 137: 232-237.
96. Zhu YX, Ahmann GJ, Bruins A, Arribas M, Chen X, Chesi M, Bergsagel PL, Fonseca R, Rimaza LM. Newly, diagnosed, untreated, multiple myeloma (MM) patient samples already harbor cereblon (CRBN) exon 10 deletions associated with drug resistance. Blood 2022; 140 (suppl.1): 4187-4188.
97. Giesien N, Paramasivam N, Toprak UK, Huebschmann D, Xu J, Uhrig S, Samur M, Bahr S,Frolich M, Mughal SS, et al. Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities. Haematologica 2022; 107: 1891-1901.
98. Ansari-Pour N, Samur M, Flynt E, Gooding S, Towfic F, Stong N, Estevez MO, Mavrommatis K, Walker B, Morgan G, et al. Whole-genome analysis identifies novel drivers and high-risk double-hit events in relapsed/refractory myeloma. Blood 2023; 141: 620-633.
99. Braunstein M, Blaney P, Morgan GJ. Whole-genome sequencing identifies structural variation as a key driver of disease relapse and aggressive clinical behavior in multiple myeloma. Blood 2023; 142 (suppl.1): 2773. Braunstein M, Blaney P, Morgan GJ. Whole-genome sequencing identifies structural variation as a key driver of disease relapse and aggressive clinical behavior in multiple myeloma. Blood 2023; 142 (suppl.1): 2773.
100. Rustad EH, Yellapantula VD, Glodzik D, Maclachlan KH, Diamond B, Boyle EM, Ashby C, Blaney P, Gundem G, Hultcrantz M, et al. Revealing the impact of structural variants in multiple myeloma. Blood Cancer Discov 2020; 1: 258-273.
101. Maclachlan KH, Rustad EH, Derkach A, Zheng-Li B, Yellapantula V, Diamond B, Hultcrantz M, Ziccheddu B, Boyle EM, Blaney P, et al. Copy number signatures predict chromotripsis and clinical outcomes in newly diagnosed multiple myeloma. Nat Commun 2021; 12: 5172.
102. Yu J, Chen N, Zheng Z, Gao M, Liang N, Wang KC. Chromotripsis detection with multiple myeloma patients based on deep graph learning. Bioinformatics 2023; 39: btads422.
103. Maclachlan KH, Ziccheddu B, Tan C, Shekarkhand T, Rueda C, Serrano E, Diamond B, Hassoun H, Mailankody S, Shah UA, et al. The complex structural variant chromotripsis can be defined on targeted sequencing panels, allowing direct clinical transition in order to improve multiple myeloma prognostication. Blood 2023; 142: 3343.
104. Maura F, Boyle EM, Rustad EH, Ashby C, Kaminetzky D, Bruno B, Braunstein M, Bauer M, Blaney P, Wang Y, Ghamalouch H, et al. Chromotripsis as a pathogenic driver of multiple myeloma. Semin Cell Dev Biol 2022; 123: 115-123.
105. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardon P, Caltagirone S, Lahuerta JJ, Facon T, et al. Revised international staging system for multiple myeloma: a report from the international myeloma working group. J Clin Oncol 2015; 33: 2863-2869.
106. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 2022; 97: 1086-1107.
107. Weinhold N, Salwender HJ, Cairn DA, Raab MS, Waldron G, Balu LW, Bertsch U, Hielscher T, Morgan GJ, Janch A, et al. Chromosome 1p21 abnormalities refine outcome prediction in patients with multiple myeloma-a meta-analysis of 2,596 patients. Haematologica 2021; 106: 2754-2758.
108. Schavgoulidze A, Lauwers-Cances V, Perrot A, Cazaubiel T, Chretien ML, Moreau P, Facon T, Leleu X, Karlin L, Stoppa AM, et al. Heterogeneity in long-term outcomes for patients with revised international staging system stage II, newly diagnosed multiple myeloma. Haematologica 2023; 108: 1374-1384.
109. D’Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall’Olio D, van de Donk D, et al. Second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma: a European myeloma network (EMN) report within the HARMONY project. J Clin Oncol 2022; 40: 3406-3418.
110. Perrot A, Lauwers-Cances V, Tournay E, Hulin C, Chretien ML, Royer B, Dib M, Decaux O, Jaccard A, Belhadij K, et al. Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol 2019; 37: 1657-1665.
111. Alzahrani K, Paslovsky O, Wang Z, Milton DR, Tanner MR, Bashir Q, Srour SA, Saini NY, Lin P, Ramdial J, et al. Impact of revised international staging system 2 (R2-ISS) risk stratification on outcomes of patients with multiple myeloma receiving autologous hematopoietic stem cell transplantation. Blood 2023; 142 (suppl. 1): 3356.
112. Guo W, Zhan A, Mary DE, Munshi MN, Makhoul O, Bally C, Zangari M, Tricot G, Peng H, Shaghnessy JD. Application of R2-ISS risk stratification to patients with multiple myeloma treated with autologous stem cell transplants at UAMS. Blood Adv 2023; 7: 6676-6684.
113. Panopoulou A, Easdale S, Ethell M, Nihcolson E, Potter M, Giotas E, Woods H, Thornton T, Pawlyn C, Boyd KD, et al. Impact of ultra high-risk genetics on real-world outcomes of transplant-eligible multiple myeloma patients. HemaSphere 2023; 7: e831.
114. Panopoulou A, Cairns DA, Holroyd A, Nichols I, Nichols I, Cray N, Pawlkyn C, Cook G, Drayson M, Boyd K, et al. Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial. Blood 2023; 141: 1666-1674.
115. Pham P, Sudha P, Wang L, Niu W, Morgan C, Ligocki C, Al-Azzawi R, Ly R, Vetrini F, Czader M, et al. Prospective molecular characterization of multiple myeloma patient samples identifies high-risk patients and informs treatment sequences through resistance mechanisms to immunotherapies. Blood 2023; 142(suppl.1): 4738.
116. Andreozzi F, Dragani M, Quivoron C, Le Bras F, Assi T, Danu A, Belhadj K, Lazarovici J, Cotteret S, Bernard OA, Ribrag V, Michot JM. Precision Medicine Approach Based on Molecular Alterations for Patients with Relapsed or Refractory Multiple Myeloma: Results from the MM-EP1 Study. Cancers (Basel). 2023 Feb 28;15(5):1508. doi: 10.3390/cancers15051508samples
Article Sidebar
Published
Jun 29, 2024
Article Details
How to Cite
Testa, U. (2024) “ RECENT ADVANCES IN THE DEFINITION OF THE MOLECULAR ALTERATIONS OCCURRING IN MULTIPLE MYELOMA: MOLECULAR ALTERATIONS OCCURRING IN MM”, Mediterranean Journal of Hematology and Infectious Diseases, 16(1), p. e2023062. doi: 10.4084/MJHID.2024.062.
Section
Review Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.