BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS MESENCHYMAL STEM CELL IN T-MN
Main Article Content
Keywords
t-MN, Bone Marrow Microenvironment, Mesenchymal Cells
Abstract
Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HSPC) by CT. However, we now know that treatment-induced mutations in HSC are not the only players involved in t-MN development but additional factors may contribute to the onset of t-MN.
One of the known drivers involved in this field is the bone marrow microenvironment (BMM) and in particular bone marrow mesenchymal stem cells (BM-MSC) whose role in t-MN pathogenesis is the topic of this mini-review.
BM-MSC, physiologically, support HSC maintenance, self-renewal, and differentiation, through hematopoietic–stromal interactions and production of cytokines. In addition, BM-MSC maintain the stability of the BM immune microenvironment and reduce the damage caused to HSC by stress stimuli.
In t-MN context, chemo/radio-therapy may induce damage to the BM-MSC and likewise alter BM-MSC functions by promoting pro-inflammatory response, clonal selection and/or the production of factors that may favor malignant hematopoiesis.
Over the last decade, it has been shown that BM-MSC isolated from patients with de novo and therapy-related MN exhibit decreased proliferative and clonogenic capacity, altered morphology, increased senescence, defective osteogenic differentiation potential, impaired immune-regulatory properties, and reduced ability to support HSC growth and differentiation, as compared to normal BM-MSC.
Although the understanding of the genetic and gene expression profile associated with ex vivo-expanded t-MN-MSCs remains limited and debatable, its potential role in prognostic and therapeutic terms is acting as a flywheel of attraction of many researchers.
Downloads
Download data is not yet available.
Abstract 928
PDF Downloads 615
HTML Downloads 84
References
1. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, Bejar R, Berti E, Busque L, Chan JKC, Chen W, Chen X, Chng WJ, Choi JK, Colmenero I, Coupland SE, Cross NCP, De Jong D, Elghetany MT, Takahashi E, Emile JF, Ferry J, Fogelstrand L, Fontenay M, Germing U, Gujral S, Haferlach T, Harrison C, Hodge JC, Hu S, Jansen JH, Kanagal-Shamanna R, Kantarjian HM, Kratz CP, Li XQ, Lim MS, Loeb K, Loghavi S, Marcogliese A, Meshinchi S, Michaels P, Naresh KN, Natkunam Y, Nejati R, Ott G, Padron E, Patel KP, Patkar N, Picarsic J, Platzbecker U, Roberts I, Schuh A, Sewell W, Siebert R, Tembhare P, Tyner J, Verstovsek S, Wang W, Wood B, Xiao W, Yeung C, Hochhaus A. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36:1703-19.
2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-405.
3. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937-51.
4. Guru Murthy GS, Hamadani M, Dhakal B, Hari P, Atallah E. Incidence and survival of therapy related myeloid neoplasm in United States. Leuk Res. 2018;71:95-99.
5. Gurnari C, Fabiani E, Falconi G, Travaglini S, Ottone T, Cristiano A, Voso MT. From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression. Biology (Basel). 2021;10:128.
6. Fianchi L, Pagano L, Piciocchi A, Candoni A, Gaidano G, Breccia M, Criscuolo M, Specchia G, Maria Pogliani E, Maurillo L, Aloe-Spiriti MA, Mecucci C, Niscola P, Rossetti E, Mansueto G, Rondoni M, Fozza C, Invernizzi R, Spadea A, Fenu S, Buda G, Gobbi M, Fabiani E, Sica S, Hohaus S, Leone G, Voso MT. Characteristics and outcome of therapy-related myeloid neoplasms: Report from the Italian network on secondary leukemias. Am J Hematol. 2015;90:E80-5. Epub 2015 Mar 3.
7. Desai P, Roboz GJ. Clonal Hematopoiesis and therapy related MDS/AML. Best Pract Res Clin Haematol. 2019;32:13-23.
8. McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017;17:513-27.
9. Swaminathan M, Bannon SA, Routbort M, Naqvi K, Kadia TM, Takahashi K, Alvarado Y, Ravandi-Kashani F, Patel KP, Champlin R, Kantarjian H, Strong L, DiNardo CD. Hematologic malignancies and Li-Fraumeni syndrome. Cold Spring Harb Mol Case Stud. 2019;5:a003210. Print 2019 Feb.
10. Schwartz JR, Ma J, Kamens J, Westover T, Walsh MP, Brady SW, Robert Michael J, Chen X, Montefiori L, Song G, Wu G, Wu H, Branstetter C, Hiltenbrand R, Walsh MF, Nichols KE, Maciaszek JL, Liu Y, Kumar P, Easton J, Newman S, Rubnitz JE, Mullighan CG, Pounds S, Zhang J, Gruber T, Ma X, Klco JM. The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms. Nat Commun. 2021;12:985.
11. Berger G, van den Berg E, Sikkema-Raddatz B, Abbott KM, Sinke RJ, Bungener LB, Mulder AB, Vellenga E. Re-emergence of acute myeloid leukemia in donor cells following allogeneic transplantation in a family with a germline DDX41 mutation. Leukemia. 2017;31:520-2.
12. Baliakas P, Tesi B, Wartiovaara-Kautto U, Stray-Pedersen A, Friis LS, Dybedal I, Hovland R, Jahnukainen K, Raaschou-Jensen K, Ljungman P, Rustad CF, Lautrup CK, Kilpivaara O, Kittang AO, Grønbæk K, Cammenga J, Hellström-Lindberg E, Andersen MK. Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up. Hemasphere. 2019;3:e321. eCollection 2019 Dec.
13. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488-98.
14. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landén M, Höglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Grönberg H, Hultman CM, McCarroll SA. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371:2477-87.
15. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley T, Link DC, Wilson RK. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015;518:552-5.
16. Voso MT, Falconi G, Fabiani E. What's new in the pathogenesis and treatment of therapy-related myeloid neoplasms. Blood. 2021;138:749-57.
17. Fabiani E, Falconi G, Fianchi L, Criscuolo M, Ottone T, Cicconi L, Hohaus S, Sica S, Postorino M, Neri A, Lionetti M, Leone G, Lo-Coco F, Voso MT. Clonal evolution in therapy-related neoplasms. Oncotarget. 2017;8:12031-40.
18. Voso MT, Pandzic T, Falconi G, Denčić-Fekete M, De Bellis E, Scarfo L, Ljungström V, Iskas M, Del Poeta G, Ranghetti P, Laidou S, Cristiano A, Plevova K, Imbergamo S, Engvall M, Zucchetto A, Salvetti C, Mauro FR, Stavroyianni N, Cavelier L, Ghia P, Stamatopoulos K, Fabiani E, Baliakas P. Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy. Br J Haematol. 2022;198:103-13.
19. Renneville A, Bernard E, Micol JB. Therapy-related myelodysplastic syndromes in the genomics era. Bull Cancer. 2023;28:S0007-4551(23)00277-1.
20. Batsivari A, Grey W, Bonnet D. Understanding of the crosstalk between normal residual hematopoietic stem cells and the leukemic niche in acute myeloid leukemia. Exp. Hematol. 2021;95:23–30.
21. Scadden DT. Nice neighborhood: Emerging concepts of the stem cell niche. Cell. 2014; 157:41–50.
22. Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. 2019;20:303–20.
23. Goulard M, Dosquet C, Bonnet D. Role of the microenvironment in myeloid malignancies. Cell Mol. Life Sci. 2018;75:1377–91
24. Mian SA, Bonnet D. Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes. Cancers (Basel). 2021;13:4116.
25. Ghobrial IM, Detappe A, Anderson KC, Steensma DP. The bone-marrow niche in MDS and MGUS: implications for AML and MM. Nat Rev Clin Oncol. 2018;15:219-33.
26. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315-7.
27. Agarwal P, Bhatia R. Influence of bone marrow microenvironment on leukemic stem cells: breaking up an intimate relationship. Adv Cancer Res. 2015;127:227–52.
28. Bulycheva E, Rauner M, Medyouf H, Theurl I, Bornhäuser M, Hofbauer LC, Platzbecker U. Myelodysplasia is in the niche: novel concepts and emerging therapies. Leukemia. 2015;29:259-68.
29. Aanei CM, Flandrin P, Eloae FZ, Carasevici E, Guyotat D, Wattel E, Campos L. Intrinsic growth deficiencies of mesenchymal stromal cells in myelodysplastic syndromes. Stem Cells Dev. 2012;21:1604–15.
30. Falconi G, Fabiani E, Fianchi L, Criscuolo M, Raffaelli CS, Bellesi S, Hohaus S, Voso MT, D'Alò F, Leone G. Impairment of PI3K/AKT and WNT/β-catenin pathways in bone marrow mesenchymal stem cells isolated from patients with myelodysplastic syndromes. Exp Hematol. 2016;44:75–83.
31. Fei C, Zhao Y, Guo J, Gu S, Li X, Chang C. Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes. Eur J Haematol. 2014;93:476–86.
32. Geyh S, Oz S, Cadeddu RP, Fröbel J, Brückner B, Kündgenet A, Fenk R, Bruns I, Zilkens C, Hermsen D, Gattermann N, Kobbe G, Germing U, Lyko F, Haas R, Schroeder T. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. Leukemia. 2013;27:1841–51.
33. Medyouf H, Mossner M, Jann JC, Nolte F, Raffel S, Herrmann C, Lier A, Eisen C, Nowak V, Zens B, Müdder K, Klein C, Obländer J, Fey S, Vogler J, Fabarius A, Riedl E, Roehl H, Kohlmann A, Staller M, Haferlach C, Müller N, John T, Platzbecker U, Metzgeroth G, Hofmann WK, Trumpp A, Nowak D. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell. 2014;14:824-37.
34. Zhao ZG, Xu W, Yu HP, Fang BL, Wu SH, Li F, Li WM, Li QB, Chen ZC, Zou P. Functional characteristics of mesenchymal stem cells derived from bone marrow of patients with myelodysplastic syndromes. Cancer Lett. 2012;317:136–43.
35. Desbourdes L, Javary J, Charbonnier T, Ishac N, Bourgeais J, Iltis A, Chomel JC, Turhan A, Guilloton F, Tarte K, Demattei MV, Ducrocq E, Rouleux-Bonnin F, Gyan E, Hérault O, Domenech J. Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis. Stem Cells Dev. 2017;26:709-22.
36. von der Heide EK, Neumann M, Vosberg S, James AR, Schroeder MP, Ortiz-Tanchez J, Isaakidis K, Schlee C, Luther M, Jöhrens K, Anagnostopoulos I, Mochmann LH, Nowak D, Hofmann WK, Greif PA, Baldus CD. Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients. Leukemia. 2017;31:1069-78.
37. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852-7.
38. Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, Westmoreland SV, Chambon P, Scadden DT, Purton LE. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell 2007;129:1097–110.
39. Rupec RA, Jundt F, Rebholz B, Eckelt B, Weindl G, Herzinger T, Flaig MJ, Moosmann S, Plewig G, Dörken B, Förster I, Huss R, Pfeffer K. Stroma mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity 2005;22:479–91.
40. Xiao P, Dolinska M, Sandhow L, Kondo M, Johansson AS, Bouderlique T, Zhao Y, Li X, Dimitriou M, Rassidakis GZ, Hellström-Lindberg E, Minato N, Walfridsson J, Scadden DT, Sigvardsson M, Qian H. Sipa1 deficiency-induced bone marrow niche alterations lead to the initiation of myeloproliferative neoplasm. Blood Adv. 2018;2:534–48.
41. Stoddart A, Wang J, Fernald AA, Davis EM, Johnson CR, Hu C, Cheng JX, McNerney ME, Le Beau MM. Cytotoxic Therapy–Induced Effects on Both Hematopoietic and Marrow Stromal Cells Promotes Therapy-Related Myeloid Neoplasms. Blood Cancer Discovery. 2020;1:32–47.
42. Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, Hoogenboezem RM, Bindels EMJ, Adisty MN, Van Strien PMH, van der Leije CS, Westers TM, Cremers EMP, Milanese C, Mastroberardino PG, van Leeuwen JPTM, van der Eerden BCJ, Touw IP, Kuijpers TW, Kanaar R, van de Loosdrecht AA, Vogl T, Raaijmakers MHGP. Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia. Cell Stem Cell. 2016;19:613-27.
43. Tothova Z, Krill-Burger JM, Popova KD, Landers CC, Sievers QL, Yudovich D, Belizaire R, Aster JC, Morgan EA, Tsherniak A, Ebert BL. Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia. Cell Stem Cell. 2017;21:547-555.e8.
44. Blau O, Hofmann WK, Baldus CD, Thiel G, Serbent V, Schümann E, Thiel E, Blau IW. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp Hematol. 2007;35:221-9.
45. Blau O, Baldus CD, Hofmann WK, Thiel G, Nolte F, Burmeister T, Türkmen S, Benlasfer O, Schümann E, Sindram A, Molkentin M, Mundlos S, Keilholz U, Thiel E, Blau IW. Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood. 2011;118:5583-92.
46. Fabiani E, Falconi G, Fianchi L, Guidi F, Bellesi S, Voso MT, Leone G, D'Alò F. Mutational analysis of bone marrow mesenchymal stromal cells in myeloid malignancies. Exp Hematol. 2014;42:731-3.
47. Jann JC, Mossner M, Riabov V, Altrock E, Schmitt N, Flach J, Xu Q, Nowak V, Obländer J, Palme I, Weimer N, Streuer A, Jawhar A, Darwich A, Jawhar M, Metzgeroth G, Nolte F, Hofmann WK, Nowak D. Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo. Nat Commun. 2021;12:6170.
48. Azuma K, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Ohyashiki K, Ohyashiki JH. Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing. Leuk Res. 2017;62:23-28.
49. Poon Z, Dighe N, Venkatesan SS, Cheung AMS, Fan X, Bari S, Hota M, Ghosh S, Hwang WYK. Bone marrow MSCs in MDS: contribution towards dysfunctional hematopoiesis and potential targets for disease response to hypomethylating therapy. Leukemia. 2019;33:1487-1500.
50. Corradi G, Baldazzi C, Očadlíková D, Marconi G, Parisi S, Testoni N, Finelli C, Cavo M, Curti A, Ciciarello M. Mesenchymal stromal cells from myelodysplastic and acute myeloid leukemia patients display in vitro reduced proliferative potential and similar capacity to support leukemia cell survival. Stem Cell Res Ther. 2018;9:271.
51. Choi H, Kim Y, Kang D, Kwon A, Kim J, Min Kim J, Park SS, Kim YJ, Min CK, Kim M. Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma. Cell Prolif. 2020;53:e12819. Epub 2020 May 5.
52. Geyh S, Rodríguez-Paredes M, Jäger P, Khandanpour C, Cadeddu RP, Gutekunst J, Wilk CM, Fenk R, Zilkens C, Hermsen D, Germing U, Kobbe G, Lyko F, Haas R, Schroeder T. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia. Leukemia. 2016;30:683-91.
53. Macedo JC, Vaz S, Bakker B, Ribeiro R, Bakker PL, Escandell JM, Ferreira MG, Medema R, Foijer F, Logarinho E. FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nat Commun. 2018;9:2834.
54. Falconi, G., Galossi, E., Fabiani, E., Pieraccioli, M., Travaglini, S., Hajrullaj, H., Cerretti, R., Palmieri, R., Latagliata, R., Maurillo, L., Voso, MT., 2022. Impairment of FOXM1 expression in mesenchymal cells from patients with myeloid neoplasms, de novo and therapy-related, may compromise their ability to support hematopoiesis. Sci Rep 12(1):21231. https://doi: 10.1038/s41598-022-24644-1.
55. Shannon K, Link DC. Soil and Seed: Coconspirators in Therapy-Induced Myeloid Neoplasms. Blood Cancer Discov. 2020;1:10-12.
56. Leone G, Fabiani E, Voso MT. De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences. Mediterr J Hematol Infect Dis. 2022;14:e2022030.
57. Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Peng J, Tang G, Goswami M, Young KH, Singh R, Medeiros LJ, Kantarjian HM, Luthra R, Wang SA. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol. 2015;8:45.
58. Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Fu B, Tang G, Goswami M, Singh R, Kanagal-Shamanna R, Pierce SA, Young KH, Kantarjian HM, Medeiros LJ, Luthra R, Wang SA. Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases. Leuk Res. 2015;39:348-54.
59. Kanagal-Shamanna R, Yin CC, Miranda RN, Bueso-Ramos CE, Wang XI, Muddasani R, Medeiros LJ, Lu G. Therapy-related myeloid neoplasms with isolated del(20q): comparison with cases of de novo myelodysplastic syndrome with del(20q). Cancer Genet. 2013;206:42-6.
60. Kutyna MM, Kok CH, Lim Y, Tran ENH, Campbell D, Paton S, Thompson-Peach C, Lim K, Cakouros D, Arthur A, Hughes T, Kumar S, Thomas D, Gronthos S, Hiwase DK. A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure. Leukemia. 2022;36:2678-89.
61. Özdemir C, Muratoğlu B, Özel BN, Alpdündar-Bulut E, Tonyalı G, Ünal Ş, Uçkan-Çetinkaya D. Multiparametric analysis of etoposide exposed mesenchymal stem cells and Fanconi anemia cells: implications in development of secondary myeloid malignancy. Clin Exp Med. 2023 May 13. Online ahead of print.
62. Gynn LE, Anderson E, Robinson G, Wexler SA, Upstill-Goddard G, Cox C, May JE. Primary mesenchymal stromal cells in co-culture with leukaemic HL-60 cells are sensitised to cytarabine-induced genotoxicity, while leukaemic cells are protected. Mutagenesis. 2021;36:419-28.
63. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644-58.
64. Suvakov S, Cubro H, White WM, Butler Tobah YS, Weissgerber TL, Jordan KL, Zhu XY, Woollard JR, Chebib FT, Milic NM, Grande JP, Xu M, Tchkonia T, Kirkland JL, Lerman LO, Garovic VD. Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia. Biol Sex Differ. 2019;10:49.
65. Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, Negley BA, Sfeir JG, Ogrodnik MB, Hachfeld CM, LeBrasseur NK, Drake MT, Pignolo RJ, Pirtskhalava T, Tchkonia T, Oursler MJ, Kirkland JL, Khosla S. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23:1072-19.
66. Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD, Tchkonia T, Kirkland JL. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging 2017;9:955–63.
67. Zoico E, Nori N, Darra E, Tebon M, Rizzatti V, Policastro G, De Caro A, Rossi AP, Fantin F, Zamboni M. Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Sci Rep. 2021;11:23237.
68. Lewis-McDougall FC, Ruchaya PJ, Domenjo-Vila E, Shin Teoh T, Prata L, Cottle BJ, Clark JE, Punjabi PP, Awad W, Torella D, Tchkonia T, Kirkland JL, Ellison-Hughes GM. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell. 2019;18:e12931. Epub 2019 Mar 10.
69. Plakhova N, Panagopoulos V, Vandyke K, Zannettino ACW, Mrozik KM. Mesenchymal stromal cell senescence in haematological malignancies. Cancer Metastasis Rev. 2023;42:277-96.
70. Bondar T, Medzhitov R. p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell. 2010;6:309–22.
2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-405.
3. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937-51.
4. Guru Murthy GS, Hamadani M, Dhakal B, Hari P, Atallah E. Incidence and survival of therapy related myeloid neoplasm in United States. Leuk Res. 2018;71:95-99.
5. Gurnari C, Fabiani E, Falconi G, Travaglini S, Ottone T, Cristiano A, Voso MT. From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression. Biology (Basel). 2021;10:128.
6. Fianchi L, Pagano L, Piciocchi A, Candoni A, Gaidano G, Breccia M, Criscuolo M, Specchia G, Maria Pogliani E, Maurillo L, Aloe-Spiriti MA, Mecucci C, Niscola P, Rossetti E, Mansueto G, Rondoni M, Fozza C, Invernizzi R, Spadea A, Fenu S, Buda G, Gobbi M, Fabiani E, Sica S, Hohaus S, Leone G, Voso MT. Characteristics and outcome of therapy-related myeloid neoplasms: Report from the Italian network on secondary leukemias. Am J Hematol. 2015;90:E80-5. Epub 2015 Mar 3.
7. Desai P, Roboz GJ. Clonal Hematopoiesis and therapy related MDS/AML. Best Pract Res Clin Haematol. 2019;32:13-23.
8. McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017;17:513-27.
9. Swaminathan M, Bannon SA, Routbort M, Naqvi K, Kadia TM, Takahashi K, Alvarado Y, Ravandi-Kashani F, Patel KP, Champlin R, Kantarjian H, Strong L, DiNardo CD. Hematologic malignancies and Li-Fraumeni syndrome. Cold Spring Harb Mol Case Stud. 2019;5:a003210. Print 2019 Feb.
10. Schwartz JR, Ma J, Kamens J, Westover T, Walsh MP, Brady SW, Robert Michael J, Chen X, Montefiori L, Song G, Wu G, Wu H, Branstetter C, Hiltenbrand R, Walsh MF, Nichols KE, Maciaszek JL, Liu Y, Kumar P, Easton J, Newman S, Rubnitz JE, Mullighan CG, Pounds S, Zhang J, Gruber T, Ma X, Klco JM. The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms. Nat Commun. 2021;12:985.
11. Berger G, van den Berg E, Sikkema-Raddatz B, Abbott KM, Sinke RJ, Bungener LB, Mulder AB, Vellenga E. Re-emergence of acute myeloid leukemia in donor cells following allogeneic transplantation in a family with a germline DDX41 mutation. Leukemia. 2017;31:520-2.
12. Baliakas P, Tesi B, Wartiovaara-Kautto U, Stray-Pedersen A, Friis LS, Dybedal I, Hovland R, Jahnukainen K, Raaschou-Jensen K, Ljungman P, Rustad CF, Lautrup CK, Kilpivaara O, Kittang AO, Grønbæk K, Cammenga J, Hellström-Lindberg E, Andersen MK. Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up. Hemasphere. 2019;3:e321. eCollection 2019 Dec.
13. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488-98.
14. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landén M, Höglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Grönberg H, Hultman CM, McCarroll SA. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371:2477-87.
15. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley T, Link DC, Wilson RK. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015;518:552-5.
16. Voso MT, Falconi G, Fabiani E. What's new in the pathogenesis and treatment of therapy-related myeloid neoplasms. Blood. 2021;138:749-57.
17. Fabiani E, Falconi G, Fianchi L, Criscuolo M, Ottone T, Cicconi L, Hohaus S, Sica S, Postorino M, Neri A, Lionetti M, Leone G, Lo-Coco F, Voso MT. Clonal evolution in therapy-related neoplasms. Oncotarget. 2017;8:12031-40.
18. Voso MT, Pandzic T, Falconi G, Denčić-Fekete M, De Bellis E, Scarfo L, Ljungström V, Iskas M, Del Poeta G, Ranghetti P, Laidou S, Cristiano A, Plevova K, Imbergamo S, Engvall M, Zucchetto A, Salvetti C, Mauro FR, Stavroyianni N, Cavelier L, Ghia P, Stamatopoulos K, Fabiani E, Baliakas P. Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy. Br J Haematol. 2022;198:103-13.
19. Renneville A, Bernard E, Micol JB. Therapy-related myelodysplastic syndromes in the genomics era. Bull Cancer. 2023;28:S0007-4551(23)00277-1.
20. Batsivari A, Grey W, Bonnet D. Understanding of the crosstalk between normal residual hematopoietic stem cells and the leukemic niche in acute myeloid leukemia. Exp. Hematol. 2021;95:23–30.
21. Scadden DT. Nice neighborhood: Emerging concepts of the stem cell niche. Cell. 2014; 157:41–50.
22. Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. 2019;20:303–20.
23. Goulard M, Dosquet C, Bonnet D. Role of the microenvironment in myeloid malignancies. Cell Mol. Life Sci. 2018;75:1377–91
24. Mian SA, Bonnet D. Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes. Cancers (Basel). 2021;13:4116.
25. Ghobrial IM, Detappe A, Anderson KC, Steensma DP. The bone-marrow niche in MDS and MGUS: implications for AML and MM. Nat Rev Clin Oncol. 2018;15:219-33.
26. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315-7.
27. Agarwal P, Bhatia R. Influence of bone marrow microenvironment on leukemic stem cells: breaking up an intimate relationship. Adv Cancer Res. 2015;127:227–52.
28. Bulycheva E, Rauner M, Medyouf H, Theurl I, Bornhäuser M, Hofbauer LC, Platzbecker U. Myelodysplasia is in the niche: novel concepts and emerging therapies. Leukemia. 2015;29:259-68.
29. Aanei CM, Flandrin P, Eloae FZ, Carasevici E, Guyotat D, Wattel E, Campos L. Intrinsic growth deficiencies of mesenchymal stromal cells in myelodysplastic syndromes. Stem Cells Dev. 2012;21:1604–15.
30. Falconi G, Fabiani E, Fianchi L, Criscuolo M, Raffaelli CS, Bellesi S, Hohaus S, Voso MT, D'Alò F, Leone G. Impairment of PI3K/AKT and WNT/β-catenin pathways in bone marrow mesenchymal stem cells isolated from patients with myelodysplastic syndromes. Exp Hematol. 2016;44:75–83.
31. Fei C, Zhao Y, Guo J, Gu S, Li X, Chang C. Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes. Eur J Haematol. 2014;93:476–86.
32. Geyh S, Oz S, Cadeddu RP, Fröbel J, Brückner B, Kündgenet A, Fenk R, Bruns I, Zilkens C, Hermsen D, Gattermann N, Kobbe G, Germing U, Lyko F, Haas R, Schroeder T. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. Leukemia. 2013;27:1841–51.
33. Medyouf H, Mossner M, Jann JC, Nolte F, Raffel S, Herrmann C, Lier A, Eisen C, Nowak V, Zens B, Müdder K, Klein C, Obländer J, Fey S, Vogler J, Fabarius A, Riedl E, Roehl H, Kohlmann A, Staller M, Haferlach C, Müller N, John T, Platzbecker U, Metzgeroth G, Hofmann WK, Trumpp A, Nowak D. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell. 2014;14:824-37.
34. Zhao ZG, Xu W, Yu HP, Fang BL, Wu SH, Li F, Li WM, Li QB, Chen ZC, Zou P. Functional characteristics of mesenchymal stem cells derived from bone marrow of patients with myelodysplastic syndromes. Cancer Lett. 2012;317:136–43.
35. Desbourdes L, Javary J, Charbonnier T, Ishac N, Bourgeais J, Iltis A, Chomel JC, Turhan A, Guilloton F, Tarte K, Demattei MV, Ducrocq E, Rouleux-Bonnin F, Gyan E, Hérault O, Domenech J. Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis. Stem Cells Dev. 2017;26:709-22.
36. von der Heide EK, Neumann M, Vosberg S, James AR, Schroeder MP, Ortiz-Tanchez J, Isaakidis K, Schlee C, Luther M, Jöhrens K, Anagnostopoulos I, Mochmann LH, Nowak D, Hofmann WK, Greif PA, Baldus CD. Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients. Leukemia. 2017;31:1069-78.
37. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852-7.
38. Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, Westmoreland SV, Chambon P, Scadden DT, Purton LE. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell 2007;129:1097–110.
39. Rupec RA, Jundt F, Rebholz B, Eckelt B, Weindl G, Herzinger T, Flaig MJ, Moosmann S, Plewig G, Dörken B, Förster I, Huss R, Pfeffer K. Stroma mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity 2005;22:479–91.
40. Xiao P, Dolinska M, Sandhow L, Kondo M, Johansson AS, Bouderlique T, Zhao Y, Li X, Dimitriou M, Rassidakis GZ, Hellström-Lindberg E, Minato N, Walfridsson J, Scadden DT, Sigvardsson M, Qian H. Sipa1 deficiency-induced bone marrow niche alterations lead to the initiation of myeloproliferative neoplasm. Blood Adv. 2018;2:534–48.
41. Stoddart A, Wang J, Fernald AA, Davis EM, Johnson CR, Hu C, Cheng JX, McNerney ME, Le Beau MM. Cytotoxic Therapy–Induced Effects on Both Hematopoietic and Marrow Stromal Cells Promotes Therapy-Related Myeloid Neoplasms. Blood Cancer Discovery. 2020;1:32–47.
42. Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, Hoogenboezem RM, Bindels EMJ, Adisty MN, Van Strien PMH, van der Leije CS, Westers TM, Cremers EMP, Milanese C, Mastroberardino PG, van Leeuwen JPTM, van der Eerden BCJ, Touw IP, Kuijpers TW, Kanaar R, van de Loosdrecht AA, Vogl T, Raaijmakers MHGP. Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia. Cell Stem Cell. 2016;19:613-27.
43. Tothova Z, Krill-Burger JM, Popova KD, Landers CC, Sievers QL, Yudovich D, Belizaire R, Aster JC, Morgan EA, Tsherniak A, Ebert BL. Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia. Cell Stem Cell. 2017;21:547-555.e8.
44. Blau O, Hofmann WK, Baldus CD, Thiel G, Serbent V, Schümann E, Thiel E, Blau IW. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp Hematol. 2007;35:221-9.
45. Blau O, Baldus CD, Hofmann WK, Thiel G, Nolte F, Burmeister T, Türkmen S, Benlasfer O, Schümann E, Sindram A, Molkentin M, Mundlos S, Keilholz U, Thiel E, Blau IW. Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood. 2011;118:5583-92.
46. Fabiani E, Falconi G, Fianchi L, Guidi F, Bellesi S, Voso MT, Leone G, D'Alò F. Mutational analysis of bone marrow mesenchymal stromal cells in myeloid malignancies. Exp Hematol. 2014;42:731-3.
47. Jann JC, Mossner M, Riabov V, Altrock E, Schmitt N, Flach J, Xu Q, Nowak V, Obländer J, Palme I, Weimer N, Streuer A, Jawhar A, Darwich A, Jawhar M, Metzgeroth G, Nolte F, Hofmann WK, Nowak D. Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo. Nat Commun. 2021;12:6170.
48. Azuma K, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Ohyashiki K, Ohyashiki JH. Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing. Leuk Res. 2017;62:23-28.
49. Poon Z, Dighe N, Venkatesan SS, Cheung AMS, Fan X, Bari S, Hota M, Ghosh S, Hwang WYK. Bone marrow MSCs in MDS: contribution towards dysfunctional hematopoiesis and potential targets for disease response to hypomethylating therapy. Leukemia. 2019;33:1487-1500.
50. Corradi G, Baldazzi C, Očadlíková D, Marconi G, Parisi S, Testoni N, Finelli C, Cavo M, Curti A, Ciciarello M. Mesenchymal stromal cells from myelodysplastic and acute myeloid leukemia patients display in vitro reduced proliferative potential and similar capacity to support leukemia cell survival. Stem Cell Res Ther. 2018;9:271.
51. Choi H, Kim Y, Kang D, Kwon A, Kim J, Min Kim J, Park SS, Kim YJ, Min CK, Kim M. Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma. Cell Prolif. 2020;53:e12819. Epub 2020 May 5.
52. Geyh S, Rodríguez-Paredes M, Jäger P, Khandanpour C, Cadeddu RP, Gutekunst J, Wilk CM, Fenk R, Zilkens C, Hermsen D, Germing U, Kobbe G, Lyko F, Haas R, Schroeder T. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia. Leukemia. 2016;30:683-91.
53. Macedo JC, Vaz S, Bakker B, Ribeiro R, Bakker PL, Escandell JM, Ferreira MG, Medema R, Foijer F, Logarinho E. FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nat Commun. 2018;9:2834.
54. Falconi, G., Galossi, E., Fabiani, E., Pieraccioli, M., Travaglini, S., Hajrullaj, H., Cerretti, R., Palmieri, R., Latagliata, R., Maurillo, L., Voso, MT., 2022. Impairment of FOXM1 expression in mesenchymal cells from patients with myeloid neoplasms, de novo and therapy-related, may compromise their ability to support hematopoiesis. Sci Rep 12(1):21231. https://doi: 10.1038/s41598-022-24644-1.
55. Shannon K, Link DC. Soil and Seed: Coconspirators in Therapy-Induced Myeloid Neoplasms. Blood Cancer Discov. 2020;1:10-12.
56. Leone G, Fabiani E, Voso MT. De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences. Mediterr J Hematol Infect Dis. 2022;14:e2022030.
57. Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Peng J, Tang G, Goswami M, Young KH, Singh R, Medeiros LJ, Kantarjian HM, Luthra R, Wang SA. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol. 2015;8:45.
58. Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Fu B, Tang G, Goswami M, Singh R, Kanagal-Shamanna R, Pierce SA, Young KH, Kantarjian HM, Medeiros LJ, Luthra R, Wang SA. Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases. Leuk Res. 2015;39:348-54.
59. Kanagal-Shamanna R, Yin CC, Miranda RN, Bueso-Ramos CE, Wang XI, Muddasani R, Medeiros LJ, Lu G. Therapy-related myeloid neoplasms with isolated del(20q): comparison with cases of de novo myelodysplastic syndrome with del(20q). Cancer Genet. 2013;206:42-6.
60. Kutyna MM, Kok CH, Lim Y, Tran ENH, Campbell D, Paton S, Thompson-Peach C, Lim K, Cakouros D, Arthur A, Hughes T, Kumar S, Thomas D, Gronthos S, Hiwase DK. A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure. Leukemia. 2022;36:2678-89.
61. Özdemir C, Muratoğlu B, Özel BN, Alpdündar-Bulut E, Tonyalı G, Ünal Ş, Uçkan-Çetinkaya D. Multiparametric analysis of etoposide exposed mesenchymal stem cells and Fanconi anemia cells: implications in development of secondary myeloid malignancy. Clin Exp Med. 2023 May 13. Online ahead of print.
62. Gynn LE, Anderson E, Robinson G, Wexler SA, Upstill-Goddard G, Cox C, May JE. Primary mesenchymal stromal cells in co-culture with leukaemic HL-60 cells are sensitised to cytarabine-induced genotoxicity, while leukaemic cells are protected. Mutagenesis. 2021;36:419-28.
63. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644-58.
64. Suvakov S, Cubro H, White WM, Butler Tobah YS, Weissgerber TL, Jordan KL, Zhu XY, Woollard JR, Chebib FT, Milic NM, Grande JP, Xu M, Tchkonia T, Kirkland JL, Lerman LO, Garovic VD. Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia. Biol Sex Differ. 2019;10:49.
65. Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, Negley BA, Sfeir JG, Ogrodnik MB, Hachfeld CM, LeBrasseur NK, Drake MT, Pignolo RJ, Pirtskhalava T, Tchkonia T, Oursler MJ, Kirkland JL, Khosla S. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23:1072-19.
66. Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD, Tchkonia T, Kirkland JL. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging 2017;9:955–63.
67. Zoico E, Nori N, Darra E, Tebon M, Rizzatti V, Policastro G, De Caro A, Rossi AP, Fantin F, Zamboni M. Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Sci Rep. 2021;11:23237.
68. Lewis-McDougall FC, Ruchaya PJ, Domenjo-Vila E, Shin Teoh T, Prata L, Cottle BJ, Clark JE, Punjabi PP, Awad W, Torella D, Tchkonia T, Kirkland JL, Ellison-Hughes GM. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell. 2019;18:e12931. Epub 2019 Mar 10.
69. Plakhova N, Panagopoulos V, Vandyke K, Zannettino ACW, Mrozik KM. Mesenchymal stromal cell senescence in haematological malignancies. Cancer Metastasis Rev. 2023;42:277-96.
70. Bondar T, Medzhitov R. p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell. 2010;6:309–22.
Article Sidebar
Published
Aug 29, 2023
Article Details
How to Cite
Voso, M. T., Falconi, G. and Fabiani, E. (2023) “BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS: MESENCHYMAL STEM CELL IN T-MN”, Mediterranean Journal of Hematology and Infectious Diseases, 15(1), p. e2023055. doi: 10.4084/MJHID.2023.055.
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.
Author Biography
Maria Teresa Voso, Università di Roma Torvergata
Istituto di Ematologia, Associate Professor