Abstract B07: Prevalence of the most common fusion gene transcripts in 1080 Egyptian pediatric acute lymphoblastic leukemia patients: Children Cancer Hospital Egypt (CCHE) experience.

Abstract

Introduction: Childhood acute lymphoblastic leukemia (ALL) is a highly heterogeneous disease with distinct biological subgroups. Objective: To detect the incidence of the most common fusion gene transcripts in a large cohort of de novo Egyptian pediatric precursor B-ALL as well as relapsed cases for the first time in Egypt. To compare our results with other Western and Eastern countries to see if there is ethnic variation. Procedure: The study included 1080 consecutive patients with de novo precursor B-ALL and 58 relapsed cases with age ≤ 18 years that were admitted and treated at Children Cancer Hospital Egypt (CCHE) from July 2007 till December 2013. Diagnosis was established by morphological examination and immunophenotyping. All cases were subjected to cytogenetic and molecular analysis. RT-PCR was carried out to test for the most common fusion gene transcripts t(12;21) ETV6/RUNX1, t(1;19) TCF3/PBX1, t(9; 22) BCR/ABL and t(4; 11) MLL/AF4. Results: Out of 1080 newly diagnosed cases, ETV6-RUNX1 was found in 165 (15.3%), E2A-PBX1 in 74 (6.9 %), BCR-ABL in 41 (3.9%) and MLL-AF4 in 20 (1.9 %). The incidence in relapsed cases was 6.7%, 6.7%, 1.7% and 5.1% respectively. As regards immunophenotyping, ETV6-RUNX1 was highly correlated with CALL, E2A-PBX to Pre-B and MLL-AF4 to Pro-B (p 0.0001, 0.0001, 0.0001) while BCR-ABL was not related to any phenotype. As regarding age, all fusion genes were highly correlated to the age group 1-10 years (p 0.0001, 0.007, 0.0001) except MLL-AF4 was correlated to 0-1 age group (p 0.0001). As regards total leucocytic count (TLC), E2A-PBX1 and BCR-ABL were correlated to < 50x103/µl and MLL-AF4 to > 100x103/µl while ETV6-RUNX1 showed no correlation. ETV6-RUNX1 (15.3%) was much lower than that reported by United States and Western Europe that have range 19-26% with a median of 23% while it is nearly comparable with Far East range of 13.4-17.5%. BCR-ABL (3.9%) is a little bit higher than western 2% while lower than Far East 6.65%. E2A-PBX1 (6.9%) was little higher than Western 3-5% and Far East 4.9%. MLL-AF4 1.9% was comparable with both Western and Far East (2-3%). Comparison with Middle East which is of limited number of studies; ETV6-RUNX1 was higher than Iraq, Kuwait, and Jordan 12.1%, 11.7%, 12% but much lower than Saudi Arabia 21%. E2A-PBX1 was much higher than Kuwait, Iraq and Saudi Arabia (1.8%, 4.2%, and 4.2%). BCR-ABL was comparable.MLL-AF4 was comparable with Saudi Arabia (2.5%) but lower than Kuwait and Iraq (3.6%, 4.2%). About relapsed cases, ETV6-RUNX1, BCR-ABL and MLL-AF4 were much lower than Western Europe and Far East. Conclusion: These frequency differences of molecular markers in childhood ALL confirm the Ethnic and geographic variation. Other factors may play a role such as exposure to environmental oncogenic factors and of course differences among laboratories may play part in this difference. So we should put into consideration that this frequency difference may have important implication for prognosis, drug selection and treatment outcome. Citation Format: Dina Yassin, Sonya Soliman, Khaled Shaaban, Sherine Salem, Nayera Hamdy, Hala Reda, Iman Sidhom, Abeer Mokhles, Nesreen Aly, Amr EL Nashar, Wafaa Rashed, Mai Mahmoud, Sarah Hesham, Alaa ELHaddad. Prevalence of the most common fusion gene transcripts in 1080 Egyptian pediatric acute lymphoblastic leukemia patients: Children Cancer Hospital Egypt (CCHE) experience. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B07.