Flowcytometric Analysis of Leukemic Blasts - as Primary Screening Test for BCR/ABL1 Gene Rearrangement in B- ALL
Objectives: Philadelphia chromosome (Ph) is common cytogenetic abnormality in B-ALL. Patients with Ph-chromosome have resistance to chemotherapy treatment with shorter event free survival, however, tyrosine kinase inhibitor (imatinib mesylate) has shown to improve the survival of Ph-positive ALL patients. The aim of the study was to examine immunophenotypic profile associated with BCR/ABL1 gene rearrangement and to put forward a model for gene rearrangement based on immunophenotypic analysis at diagnosis. Methods: We had carried out a retrospective analysis of 130 patients with B-ALL diagnosed at The Gujarat Cancer and Research Institute. Immunophenotyping of leukemic blasts was carried out using flowcytometry and BCR/ABL1 fusion gene was detected by FISH analysis. Results: BCR/ABL1 fusion was observed in 24% of B-ALL. All patients with BCR/ABL1 gene rearrangement were positive for CD10 and Tdt. BCR/ABL1-positive cases exhibited a greater MFI value of Tdt, CD10, CD34, CD13, CD33, but a lower MFI value of CD22, CCD79a as compared to BCR/ABL1 negative cases. Multivariate logistic regression analysis showed that high MFI of Tdt, CD10 and low MFI of CD22 and CCD79a predict the presence of BCR/ABL1 rearrangement. Conclusion: Immunophenotypic profile of B-ALL patients can be used as primary screening to predict occurrence of BCR/ABL1 gene rearrangement.
1.EG van Lochem, VHJ van der Velden, HK Wind, et al. Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts. Cytometry Part B (Clinical Cytometry) 2004;60B:1–13.[CrossRef]
2. Voncken JW, Kaartinen V, Pattengale PK, Germeraad WT, Groffen J, Heisterkamp N. BCR/ABL1 P210 and P190 cause distinct leukemia in transgenic mice. Blood 1995;86:4603-11.
3. Gotz G, Weh HJ, Walter TA, Kuse R, Kolbe K, Dolken G, et al. Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia. Ann Hematol 1992;64:97-100. [CrossRef]
4. Roberts WM, Rivera GK, Raimondi SC, Santana VM, Sandlund JT, Crist WM, et al. Intensive chemotherapy for Philadelphiachromosome-positive acute lymphoblastic leukaemia. Lancet 1994;343:331-2. [CrossRef]
5. Faderl S, Kantarjian HM, Thomas DA, Cortes J, Giles F, Pierce S, et al. Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Leuk Lymphoma 2000;36:263-73.
6. Fuster JL, Bermudez M, Galera A, Llinares ME, Calle D, Ortuno FJ. Imatinib mesylate in combination with chemotherapy in four children with de novo and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica 2007;92:1723-4.[CrossRef]
7. Tabernero MD, Bortoluci AM, Alaejos I, Lopez-Berges MC, Rasillo A, Garcia-Sanz R, et al. Adult precursor B-ALL with BCR/ ABL1 gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expresssion. Leukemia 2001;15:406-14. [CrossRef]
8. Kalina T, Vaskova M, Mejstrikova E, Madzo J, Trka J, Stary J, et al. Myeloid antigens in childhood lymphoblastic leukemia: clinical data point to regulation of CD66c distinct from other myeloid antigens. BMC Cancer 2005;5:38.[CrossRef]
9. Hrusak O, Trka J, Zuna J, Houskova J, Bartůnkova J, Stary J. Aberrant expression of KORSA3544 antigen in childhood acute lymphoblastic leukemia predicts TEL-AML1 negativity. The Pediatric Hematology Working Group in the Czech Republic. Leukemia 1998;12:1064-70. [CrossRef]
10. Owaidah TM, Rawas FI, Al Khayatt MF, Elkum NB. Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL1 rearrangement. Hematol Oncol Stem Cell Ther 2008;1:34-7[CrossRef]
11. Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol 2009;27:5175-81.[CrossRef]
12. Radich JP. Philadelphia chromosome-positive acute lymphocytic leukemia. Hematol Oncol Clin North Am 2001;15:21-36.
13. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia positive acute lymphoblastic leukaemia in adults – age distribution, BCR breakpoint and prognostic significance. Leukemia 1991;5:196–9.
14. Annino L, Ferrari A, Cedrone M, Giona F, Lo Coco F, Meloni G, Arcese W, Mandelli F. Adult Philadelphia-chromosome-positive acute lymphoblastic leukaemia: experience of treatments during a 10-year period. Leukemia 1994;8:664–7.
15. Secker-Walker LM, Pentrice HG, Durrant J, Richards S, Hall E, Harrison G. Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. Br J Haematol 1997;96:601–10. [CrossRef]
16. Pui CH, Crist WM, Look T. Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukaemia. Blood 1990;76:1449–63.
17. Annino L, Ferrari A, Cedrone M, Giona F, Lo Coco F, Meloni G, et al. Adult Philadelphia-chromosome-positive acute lymphoblastic leukaemia: experience of treatments during a 10-year period. Leukemia 1994;8:664–7.
18. Francesco Corrente and Silvia Bellesi, Elisabetta Metafuni, Pier Luigi Puggioni, Sara Marietti, Angela Maria Ciminello, Tommaso Za, Federica Sora, Luana Fianchi, Simona Sica, Valerio De Stefano, Patrizia Chiusolo Role of flow-cytometric immunophenotyping in prediction of BCR/ABL1 gene rearrangement in adult B-cell acute lymphoblastic Leukemia, Cytometry B Clin Cytom 2018;94:468-76.[CrossRef]
