Abstract B038: RT-PCR and Interphase FISH reveal high frequencies of BCR-ABL in pediatric ALL patients in South-East Asia

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Fusion oncogenes (FOs) caused by chromosomal abnormalities play a significant role in the development, prognostic stratification and treatment decision-making of pediatric B cell acute lymphoblastic leukemia (ALL). The predominant fusion oncogenes (FOs) in ALL include BCR-ABL, MLL-AF4, ETV6-RUNX1, and TCF3-PBX1, all of which carry significant prognosis and treatment selection implications. Furthermore, the frequency of FOs exhibit ethnic variation. Pediatric ALL has poorer outcome in Pakistan as compared to global outcome for which reasons are unknown. To find out the genetic basis of this, we carried out molecular cytogenetic analysis of pediatric ALL in Pakistani population. We studied FOs of clinical importance, clinical presentation, and outcome in pediatric B-ALL in Pakistan. The study included 188 ALL patients and employed reverse transcriptase-polymerase chain reaction (RT-PCR) and results verified using interphase fluorescence in situ hybridization (FISH). The data were analyzed using SPSS version 25. Results: FOs were identified in 87.2% of the individuals. The average overall survival was 70.9 weeks, with a 3-year survival rate of 31.9% and a 3-year relapse-free survival rate of 18.1%. Four individuals succumbed to medication toxicities. ETV6-RUNX1 (19.14 %) demonstrated a higher survival rate (110.9 weeks; p = 0.03). TCF3-PBX1 (2.1 %) was linked to a worse outcome and an increased risk of relapse in the central nervous system (CNS). MLL-AF4 (18.1 %) was more prevalent in the 8- to 15-year age group (24/34; p = 0.001) and was associated with organomegaly, low platelet count, and poor survival. BCR-ABL (47.9 %) was associated with older age (7–15 years, 52/90), lower remission rates, shorter survival (43.73 ± 4.24 weeks), and a higher white blood cell count. MLL-AF4 and BCR-ABL were found in 66% of B-ALL cases, which typically occur in older children. This study reveals that the occurrence of BCR-ABL FO in pediatric ALL within a specific ethnic group is the highest ever reported. These findings align with earlier studies conducted in our region. Two-thirds of pediatric B-ALL cases in South-East Asia have been shown to have a bad prognosis due to the presence of BCR-ABL and MLL-AF4. This is likely the cause of the previously reported low survival rates for childhood ALL in this region. Additionally, the integration of tyrosine kinase inhibitors and hematopoietic stem cell transplantation facilities should be implemented to enhance treatment outcomes for patients in developing nations. Citation Format: Sarah Almukhaylid, Zafar Iqbal, Nawaf Alanzazi. RT-PCR and Interphase FISH reveal high frequencies of BCR-ABL in pediatric ALL patients in South-East Asia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B038.