SPECTRUM AND IMMUNOPHENOTYPIC PROFILE OF ACUTE LEUKEMIA: A TERTIARY CENTER FLOW CYTOMETRY EXPERIENCE
Main Article Content
Keywords
AML; MPAL; B-ALL; T-ALL; FLT3/NPM1c; AUL
Abstract
Introduction: For diagnosis, sub-categorization and follow up of Acute Leukemia (AL), phenotypic analysis using flow cytometry is mandatory.
Material and methods: We retrospectively analyzed immunophenotypic data along with cytogenetics/molecular genetics data (wherever available) from 631 consecutive cases of AL diagnosed at our flow cytometry laboratory from January 2014 to August 2017.
Results: Of the total 631 cases, 52.9% (n=334) were acute lymphoblastic leukemia (ALL), 43.9% (n=277) acute myeloid leukemia (AML), 2.2% (n=14) mixed phenotypic acute leukemia (MPAL) and0.5% (n=3) each of acute undifferentiated leukemia (AUL) and chronic myeloid leukemia in blast crisis (CML-BC). ALL cases comprised of 81.7% (n=273/334) B-cell ALLs (95.2%, n=260/273 common B-ALLs and 4.8%, n=13/273 Pro B-ALLs). CD13 was the commonest cross lineage antigen expressed in B-ALL (25.6%), followed by CD33 (17.9%) and combined CD13/CD33 (11.3%) expression. T-ALLs constituted 18.3% (n=61/334) of total ALLs and included 27.9% (n=17) cortical T- ALLs. CD13 was commonest (32.7%) aberrantly expressed antigen in T-ALLs, followed by CD117 (16.0%). AML cases included 32.1% (n=89/277) AML with recurrent genetic abnormalities, 9.0% (n=25/277) with FLT3/NPM1c mutation and 58.9% (n=163/277) AML NOS including 14.7% (n=24/163) AML M4/M5, 1.8% (n=3/163) AML M6 and 3.7% (n=6/163) AML M7. In AMLs, CD19 aberrancy was the most common (16.3%) followed by CD7 (11.9%).
Conclusion: In this study we document the spectrum; correlate the immunophenotype with genetic data of all leukemias, especially with respect to T-ALL where the data from India is scarce.
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References
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13. Nakase K, Bradstock K, Sartor M, Gottlieb D, Byth K, Kita K, Shiku H, Kamada N. Geographic heterogeneity of cellular characteristics of acute myeloid leukemia: a comparative study of Australian and Japanese adult cases. Leukemia. 2000 Jan 1;14(1):163.
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24. Seegmiller AC, Kroft SH, Karandikar NJ, McKenna RW. Characterization of immunophenotypic aberrancies in 200 cases of B acute lymphoblastic leukemia. American journal of clinical pathology. 2009 Dec 1;132(6):940-9.
25. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, Mangioni S, Schrappe M, Riehm H, Lampert F, Basso G. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Blood. 1997 Jul 15;90(2):571-7.
26. Yang C, Yang LH, Zhang RJ, Ge XY, Wang MF, Ren FG, Zhang YF, Hou YF, Wang YP. Expression of CD25 in acute B cell lymphoblastic leukemia and its clinical significance. Zhongguo shi yan xue ye xue za zhi. 2014 Jun;22(3):634-9.
27. Kumar J, Khan AA, Saraf A, Bhargava M. Expression of CD20 in B Cell Precursor Acute Lymphoblastic Leukemia. Indian Journal of Hematology and Blood Transfusion. 2014 Mar 1;30(1):16-8.
28. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45.
29. Basso G, Lanza F, Orfao A, Moretti S, Castoldi G. Clinical and biological significance of CD34 expression in acute leukemia. Journal of biological regulators and homeostatic agents. 2001 Jan 1;15(1):68-78.
30. Dakka N, Bellaoui H, Bouzid N, Khattab M, Bakri Y, Benjouad A. CD10 AND CD34 expression in childhood acute lymphoblastic leukemia in Morocco: clinical relevance and outcome. Pediatric hematology and oncology. 2009 Jan 1;26(4):216-31.
31. Jain N, Lamb AV, O’Brien S, Ravandi F, Konopleva M, Jabbour E, Zuo Z, Jorgensen J, Lin P, Pierce S, Thomas D. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016 Apr 14;127(15):1863-9.
32. Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterranean journal of hematology and infectious diseases. 2014;6(1).
33. Webber BA, Cushing MM, Li S. Prognostic significance of flow cytometric immunophenotyping in acute myeloid leukemia. International journal of clinical and experimental pathology. 2008;1(2):124.
34. Legrand O, Perrot JY, Baudard M, Cordier A, Lautier R, Simonin G, Zittoun R, Casadevall N, Marie JP. The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score. Blood. 2000 Aug 1;96(3):870-7.
35. Osman IM, Humeida AA, Eltayeb O, Abdelrhman I, Elhadi TA. Flowcytometric Immunophenotypic characterization of acute myeloid leukemia (AML) in Sudan. International Journal of Hematological Disorders. 2015 Jan 23;2(1):10-7.
36. Khalidi HS, Medeiros LJ, Chang KL, Brynes RK, Slovak ML, Arber DA. The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities. American Journal of Clinical Pathology. 1998 Feb 1;109(2):211-20.
37. Sainty D, Liso V, Cantù-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, Benattar L, Fenu S, Mancini M, Duchayne E, Mahon FX. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlyingPLZF/RARA gene rearrangements. Blood. 2000 Aug 15;96(4):1287-96.
38. Ortolani C. Flow cytometry of hematological malignancies. John Wiley & Sons; 2011 Aug 15.
39. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G. Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine. 2016 Jun 9;374(23):2209-21.
40. Matutes E, Pickl WF, van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011 Mar 17;117(11):3163-71.
41. Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, Drexler HG, MacLeod RA, Wu D, Chen S. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica. 2012 Nov 1;97(11):1708-12.
42. Eckstein OS, Wang L, Punia JN, Kornblau SM, Andreeff M, Wheeler DA, Goodell MA, Rau RE. Mixed-phenotype acute leukemia (MPAL) exhibits frequent mutations in DNMT3A and activated signaling genes. Experimental hematology. 2016 Aug 1;44(8):740-4.
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 (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016 Jan 1:blood-2016Paietta E. Immunobiology of acute leukemia. In Neoplastic Diseases of the Blood 2013 (pp. 241-283). Springer New York.
3. Bain, Barbara J., Imelda Bates, and Mike A. Laffan. Dacie and Lewis Practical Haematology E-Book. Elsevier Health Sciences, 2016.
4. Korf BR. Overview of clinical cytogenetics. Current Protocols in Human Genetics. 2001 Aug:8-1.
5. Leonard DG, Bagg A, Caliendo AM, Deerlin VM, Kaul KL, editors. Molecular pathology in clinical practice. Springer Science+ Business Media, LLC; 2007 Nov 25.
6. Pawar RN, Banerjee S, Bramha S, Krishnan S, Bhattacharya A, Saha V, Chakrapani A, Bhave S, Chandy M, Nair R, Parihar M. Mixed-phenotypic acute leukemia series from tertiary care center. Indian Journal of Pathology and Microbiology. 2017 Jan 1;60(1):43.
7. Gujral S, Badrinath Y, Kumar A, Subramanian PG, Raje G, Jain H, Pais A, Kadam PS, Banavali SD, Arora B, Kumar P. Immunophenotypic profile of acute leukemia: critical analysis and insights gained at a tertiary care center in India. Cytometry Part B: Clinical Cytometry. 2009 May 1;76(3):199-205.
8. Ghosh S, Shinde SC, Kumaran GS, Sapre RS, Dhond SR, Badrinath Y, Ansari R, Kumar A, Mahadik S, Chougule AB, Nair CN. Haematologic and immunophenotypic profile of acute myeloid leukemia: an experience of Tata Memorial Hospital. Indian journal of cancer. 2003 Apr 1;40(2):71.
9. Advani S, Pai S, Venzon D, Adde M, Kurkure PK, Nair CN, Sirohi B, Banavali SD, Hawaldar R, Kolhatkar BB, Vats T. Acute lymphoblastic leukemia in India: an analysis of prognostic factors using a single treatment regimen. Annals of oncology. 1999 Feb;10(2):167-76.
10. El Sharkawy N, Abdel Hamid T. Internal tandem duplication of FLT3 gene in Egyptian adult acute myeloid and acute lymphoblastic leukemia. J Am Sci. 2010;6(9):14-22.
11. Salah SM. Detection of CXCL12 gene polymorphism and CXCR4 receptor expressionin Egyptian acute myeloid leukemia patients.
12. Salem DA, El-Aziz SM. Flowcytometric immunophenotypic profile of acute leukemia: mansoura experience. Indian journal of hematology and blood transfusion. 2012 Jun 1;28(2):89-96.
13. Nakase K, Bradstock K, Sartor M, Gottlieb D, Byth K, Kita K, Shiku H, Kamada N. Geographic heterogeneity of cellular characteristics of acute myeloid leukemia: a comparative study of Australian and Japanese adult cases. Leukemia. 2000 Jan 1;14(1):163.
14. Chang H, Salma F, Yi QL, Patterson B, Brien B, Minden MD. Prognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia. Leukemia research. 2004 Jan 31;28(1):43-8.
15. Wang XB, Zheng JE, Gu JX, Yao JX, Yang J, Liu J, Li XQ, He YL, Yu JM, Wei J, Liu ZP. Correlation of immunophenotype to cytogenetics and clinical features of adult acute myeloid leukemia. Ai zheng= Aizheng= Chinese journal of cancer. 2005 Jun;24(6):667-71.
16. Dong HY, Kung JX, Bhardwaj V, McGill J. Flow cytometry rapidly identifies all acute promyelocytic leukemias with high specificity independent of underlying cytogenetic abnormalities. American journal of clinical pathology. 2011 Jan 1;135(1):76-84.
17. Bachir F, Bennani S, Lahjouji A, Cherkaoui S, Khattab M, Nassereddine I, Zafad S, El Aouad R. Characterization of acute lymphoblastic leukemia subtypes in Moroccan children. International journal of pediatrics. 2009 Jul 19;2009.
18. Bhushan B, Chauhan PS, Saluja S, Verma S, Mishra AK, Siddiqui S, Kapur S. Aberrant phenotypes in childhood and adult acute leukemia and its association with adverse prognostic factors and clinical outcome. Clinical and experimental medicine. 2010 Mar 1;10(1):33-40.
19. Vitale A, Guarini A, Ariola C, Meloni G, Perbellini O, Pizzuti M, De Gregoris C, Mettivier V, Pastorini A, Pizzolo G, Vignetti M. Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial. Haematologica. 2007 Mar 1;92(3):342-8.
20. Shen HQ, Tang YM, Yang SL, Qian BQ, Song H, Shi SW, Xu WQ. Immunophenotyping of 222 children with acute leukemia by multi-color flow cytometry. Zhonghua er ke za zhi= Chinese journal of pediatrics. 2003 May;41(5):334-7.
21. Woo JS, Alberti MO, Tirado CA. Childhood B-acute lymphoblastic leukemia: a genetic update. Experimental hematology & oncology. 2014 Jun 13;3(1):16.
22. Velizarova M, Popova D, Hadjiev E, Aleksandrova K, Dimova I, Zaharieva B, Toshkov S, Staneva M, Hodjajik D, Penev M, Toncheva D. Molecular-cytogenetic aberrations in B-cell adult acute lymphoblastic leukemia (B-ALL)-frequency and correlation with immunophenotype. Turk J Hematol. 2006 Sep 5;23:151-7.
23. Supriyadi E, Veerman AJ, Purwanto I, Cloos J. Myeloid antigen expression in childhood acute lymphoblastic leukemia and its relevance for clinical outcome in indonesian ALL-2006 protocol. Journal of oncology. 2012 Nov 26;2012.
24. Seegmiller AC, Kroft SH, Karandikar NJ, McKenna RW. Characterization of immunophenotypic aberrancies in 200 cases of B acute lymphoblastic leukemia. American journal of clinical pathology. 2009 Dec 1;132(6):940-9.
25. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, Mangioni S, Schrappe M, Riehm H, Lampert F, Basso G. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Blood. 1997 Jul 15;90(2):571-7.
26. Yang C, Yang LH, Zhang RJ, Ge XY, Wang MF, Ren FG, Zhang YF, Hou YF, Wang YP. Expression of CD25 in acute B cell lymphoblastic leukemia and its clinical significance. Zhongguo shi yan xue ye xue za zhi. 2014 Jun;22(3):634-9.
27. Kumar J, Khan AA, Saraf A, Bhargava M. Expression of CD20 in B Cell Precursor Acute Lymphoblastic Leukemia. Indian Journal of Hematology and Blood Transfusion. 2014 Mar 1;30(1):16-8.
28. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45.
29. Basso G, Lanza F, Orfao A, Moretti S, Castoldi G. Clinical and biological significance of CD34 expression in acute leukemia. Journal of biological regulators and homeostatic agents. 2001 Jan 1;15(1):68-78.
30. Dakka N, Bellaoui H, Bouzid N, Khattab M, Bakri Y, Benjouad A. CD10 AND CD34 expression in childhood acute lymphoblastic leukemia in Morocco: clinical relevance and outcome. Pediatric hematology and oncology. 2009 Jan 1;26(4):216-31.
31. Jain N, Lamb AV, O’Brien S, Ravandi F, Konopleva M, Jabbour E, Zuo Z, Jorgensen J, Lin P, Pierce S, Thomas D. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016 Apr 14;127(15):1863-9.
32. Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterranean journal of hematology and infectious diseases. 2014;6(1).
33. Webber BA, Cushing MM, Li S. Prognostic significance of flow cytometric immunophenotyping in acute myeloid leukemia. International journal of clinical and experimental pathology. 2008;1(2):124.
34. Legrand O, Perrot JY, Baudard M, Cordier A, Lautier R, Simonin G, Zittoun R, Casadevall N, Marie JP. The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score. Blood. 2000 Aug 1;96(3):870-7.
35. Osman IM, Humeida AA, Eltayeb O, Abdelrhman I, Elhadi TA. Flowcytometric Immunophenotypic characterization of acute myeloid leukemia (AML) in Sudan. International Journal of Hematological Disorders. 2015 Jan 23;2(1):10-7.
36. Khalidi HS, Medeiros LJ, Chang KL, Brynes RK, Slovak ML, Arber DA. The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities. American Journal of Clinical Pathology. 1998 Feb 1;109(2):211-20.
37. Sainty D, Liso V, Cantù-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, Benattar L, Fenu S, Mancini M, Duchayne E, Mahon FX. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlyingPLZF/RARA gene rearrangements. Blood. 2000 Aug 15;96(4):1287-96.
38. Ortolani C. Flow cytometry of hematological malignancies. John Wiley & Sons; 2011 Aug 15.
39. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G. Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine. 2016 Jun 9;374(23):2209-21.
40. Matutes E, Pickl WF, van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011 Mar 17;117(11):3163-71.
41. Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, Drexler HG, MacLeod RA, Wu D, Chen S. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica. 2012 Nov 1;97(11):1708-12.
42. Eckstein OS, Wang L, Punia JN, Kornblau SM, Andreeff M, Wheeler DA, Goodell MA, Rau RE. Mixed-phenotype acute leukemia (MPAL) exhibits frequent mutations in DNMT3A and activated signaling genes. Experimental hematology. 2016 Aug 1;44(8):740-4.