High frequency of BCR-ABL oncogene in pediatric acute lymphoblastic leukemia (ALL) patients as revealed by RT-PCR and interphase FISH: Association with disease biology and treatment outcome

Autor: Ammara H Tahir, Sumrin Sahar, Noreen Sabir, Tanveer Akhtar, Tashfin Awan, Zafar Iqbal, Aamer Aleem, Sultan Asad, Mohammad Hasan Siddique, Mudassar Iqbal
Rok vydání: 2012
Předmět:
Zdroj: Journal of Clinical Oncology. 30:6612-6612
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2012.30.15_suppl.6612
Popis: 6612 Background: ALL is a complex genetic disease involving many fusion oncogenes (FGs)1 frequency of which can vary in different ethnic groups2,3 thus having implication in differential diagnosis, prognosis and treatment. Methods: We studied FGs in 101 pediatric ALL patients using RT-PCR1 at Day 0, Day 15 and Day 29 and Interphase FISH, and their association with clinical features and treatment outcome. Results: Five most common FGs i.e. BCRABL (t 22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 88.1% (89/101) patients. Frequency of BCR-ABL was 44.5% (45/101). Patients with BCR-ABL had significantly lower survival (43.733 weeks ±4.241) as compared to others except MLL-AF4 and significantly higher TLC count. Overall survival was lower (52.2±3.75) than the patients with ETV6-RUN X 1 (65.2± 9.9) which may be due to overall high frequency of poor prognostic FGs (71%) as compared to ETV6-RUNX 1 (17.1%) (p=0.01). Conclusions: This is the first study from Pakistan correlating molecular markers, disease biology and treatment response. It is the highest reported frequency of BCR-ABL in pediatric ALL and was associated with disease biology and survival. Some authors have reported BCR-ABL frequency higher than in West2,4,5 while others reported 45% frequency of ETV6-RUNX16. These and our data reflect strong interplay of genetic and environmental factors in biology of pediatric ALL and its correlation with disease biology and treatment2,3. Our data indicates immediate need for large clinical trials of imatinib, dasatinib and nilotinib in paediatric ALL treatment in our ethnic group. This study will lead to unravel the mechanisms of BCR-ABL Leukemogenesis and to find population-specific biomarkers and drug targets. References: 1) van Dongen JJ, et al., Leukemia. 1999 Dec; 13(12):1901-28. 2) Iqbal Z, et al. J Pediatr Hematol Oncol. 2007 Aug; 29(8):585. 3) Ariffin H, et al. J Pediatr Hematol Oncol. 2007 Jan; 29(1):27-31. 4) Ramos C, et al. 2011 Sep; 139(9):1135-42. 5) Artigas A CG, et al. Rev Med Chil. 2006 Nov; 134(11):1367-76. 6) Karrman K, et al. Br J Haematol. 2006 Nov; 135(3):352-4.
Databáze: OpenAIRE
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