The Profile of BCR-ABL1 Fusion Gene in Childhood Leukemia at “Dharmais” Cancer Hospital
Background: BCR-ABL1 fusion gene, which originated from t (9;22), is an important biomarker for diagnosis, therapeutic approach, and prognosis in childhood leukemia. However, there are no data in Indonesia about the profile of BCR-ABL1 fusion gene for this disease. This study intends to demonstrate the profile of the BCR-ABL1 fusion gene in childhood leukemia at “Dharmais” Cancer Hospital.
Methods: This descriptive retrospective study included 79 patients with childhood leukemia who performed the BCR-ABL1 examination in “Dharmais” Cancer Hospital during 2008–2018. Demographic data, leukemia types, BCR-ABL1 examination results, and protein isoforms developed by BCR-ABL1 fusion were obtained from Cancer Registry Data.
Results: Among 79 patients’ data recorded in this study, 65.8% (52/79) were male and 34.2% (27/79) were female. A total of 74.7% (59/79) patients were diagnosed with Chronic Myelogenous Leukemia (CML), 21.5% (17/79) with Acute Lymphoblastic Leukemia (ALL), and 3.8% (3/79) with Acute Myelogenous Leukemia (AML). The profile of positive BCR-ABL1 in CML patients was 72.8% (43/59). About 97.7% (42/43) of CML patients with positive BCR-ABL1 fusion gene expressed 210-kDa protein, while only 2.3% (1/43) expressed 190-kDa protein.
Conclusions: This study found that, from a total of 79 respondents, 45 of them showed a positive BCR-ABL result, with details of 43 in CML and 2 in ALL. Among the total of 43 CML patients with positive BCR-ABL1, 42 (97.7%) of them expressed 210-kDa protein isoform. Further research to investigate the relationship between protein isoforms and their clinical effects may also be important to discuss. The valuable recommendation suggests that BCR-ABL1 examination should be performed for all childhood leukemia patients in Indonesia, especially for CML and ALL.
Rubnitz, Jeffrey E., Look AT. Molecular genetics of childhood leukemias. J Pediatr Hematol Oncol.1998;20(1);1–11.
Damjanov I. Neoplasia. In: Pathology Secrets. Elsevier; 2009. p. 76–97.
Score J, Calasanz MJ, Ottman O, Pane F, Yeh RF, Sobrinho-Simões MA, et al. Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation. Leukemia. 2010;24(10):1742–50.
Harvey RC, Tasian SK. Clinical diagnostics and treatment strategies for Philadelphia chromosome-like acute lymphoblastic leukemia. Blood Adv. 2020;4(1):218–28.
Boer JM, Steeghs EMP, Marchante JRM, Boeree A, Beaudoin JJ, Beverloo HB, et al. Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia. Oncotarget. 2017;8(3):4618–28.
Harrison CJ. Philadelphia Chromosome. In: Encyclopedia of Genetics. Elsevier; 2001. p. 1449–50.
Hutter JJ. Childhood Leukemia. Pediatr Rev. 2010;31(6):234–41.
Zhen C, Wang YL. Molecular Monitoring of Chronic Myeloid Leukemia. J Mol Diagnostics. 2013;15(5):556–64.
Cazzaniga G, Lanciotti M, Rossi V, Di Martino D, Aricò M, Valsecchi MG, et al. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response. Br J Haematol. 2002;119(2):445–53.
Neuendorff NR, Burmeister T, Dörken B, Westermann J. BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features. Ann Hematol. 2016;95(8):1211–21.
Koo HH. Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood. Korean J Pediatr. 2011;54(3):106–10.
Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008;112(2):416–32.
Crist W, Carroll A, Shuster J, Jackson J, Head D, Borowitz M, et al. Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study. Blood. 1990;76(3):489–94.
Cutler JA, Tahir R, Sreenivasamurthy SK, Mitchell C, Renuse S, Nirujogi RS, et al. Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis. Leukemia. 2017;31(7):1513–24.
Reckel S, Hamelin R, Georgeon S, Armand F, Jolliet Q, Chiappe D, et al. Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics. Leukemia. 2017;31(7):1502–12.
Tasian SK, Loh ML, Hunger SP. Philadelphia chromosome–like acute lymphoblastic leukemia. Blood. 2017;130(19):2064–72.
Roberts KG, Reshmi SC, Harvey RC, Chen IM, Patel K, Stonerock E, et al. Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the children’s oncology group. Blood. 2018;132(8):815–24.
Ilaria RL, Van Etten RA. The SH2 domain of P210BCR/ABL is not required for the transformation of hematopoietic factor-dependent cells. Blood. 1995;86(10):3897–904.
Lugo TG, Pendergast A, Muller AJ. Tyrosine Kinase Activity and Transformation Potency of bcr-abl Oncogene Products. Int J Oncol.
An X, Tiwari AK, Sun Y, Ding PR, Ashby CR, Chen ZS. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: A review. Leuk Res. 2010;34(10):1255–68.
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