Biological Systems: Open Access

ISSN - 2329-6577


High frequency and poor prognosis of late childhood BCR-ABL positive and MLL-AF4 positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan

3rd International Conference on Integrative Biology

August 04-06, 2015 Valencia, Spain

Zafar Iqbal

Posters-Accepted Abstracts: Biol Syst Open Access

Abstract :

Background: Fusion oncogenes (FO�??s) resulting from chromosomal abnormalities have important role in leukemogenesis in pediatric B-cell acute lymphoblastic leukemia (ALL). The most common FO�??s are BCR-ABL, MLL-AF4, ETV6-RUNX1 and TCF3-PBX1 which have important prognostic and drug selection implications. Moreover, frequencies of FO�??s have ethnic variations. We studied frequencies of FO�??s, clinical pattern and outcome in pediatric B-ALL. Methods: FO�??s were studied in 188 patients at diagnosis using RT-PCR and inter-phase FISH. Data were analyzed using SPSS version 17. Results: FO�??s were detected in 87.2% of patients. Mean overall survival was 70.9 weeks, 3-year survival 31.9% and 3-year relapse free survival 18.1%. Four patients died of drug toxicities. ETV6-RUNX1 (19.14%) had better survival (110.9 weeks, p=0.03). TCF3-PBX1 (2.1%) was associated with inferior outcome and higher CNS relapse risk. MLL-AF4 (18.1%) was more common in 8-15 year age group (24/34, p=0.001) and 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 higher white cell count. Overall, MLL-AF4 and BCR-ABL were detected in 66% of B-ALL presented at later childhood and were associated with poor prognosis and inferior survival. Conclusions: Study reports highest frequency of BCR-ABL FO in pediatric ALL consistent with the previous reports from our region. Poor prognosis BCR-ABL and MLL-AF4 detected in two third pediatric B-ALL are likely to be the reason for alreadyreported poor survival in our part of the world. Furthermore, MLL-AF4 usually most common in infants presented at late childhood in most of ALL patients which is one of the unique findings in our study. This highlights the need for mandatory inclusion of molecular testing for pediatric ALL patients in clinical decision making and incorporation of TKIs as well as HSCT facilities to improve treatment outcome in developing countries.