Cytogenetics and Molecular Genetics in Pediatric Acute Lymphoblastic Leukemia (ALL) and Its Correlation with Induction Outcomes.

Abstract

Arathi SrinivasanAims  The aim was to study cytogenetics and molecular genetic profile in pediatric B-acute lymphoblastic leukemia (ALL) and correlate it with induction outcomes. Subjects and Methods  A retrospective study of cytogenetics and molecular genetics of 98 children with B-cell ALL from January 2013 to May 2018 was done. Cytogenetics and molecular genetics were done in the bone marrow using multiplex reverse transcription polymerase chain reaction and G-banded karyotyping, respectively. Minimal residual disease (MRD) assessment was done at the end of induction by flowcytometry. Results  Of the 98 children, 83 (84.6%) had evaluable cytogenetics, with 11 (13.25%) being abnormal karyotypes. Of the 11 abnormal karyotypes, seven children (8.4%) had hyperdiploidy, one had hypodiploidy, and three had miscellaneous findings. In molecular genetics, TEL-AML1 (ETV6/RUNX1)[t(12;21)] was the most common fusion gene abnormality (12.2% [12/98]), followed by E2A-PBX1 [t(1;19)] (5%), BCR/ABL1 [t(9;22)] (3%), and MLL-AF4 [t(4;11)] (1%). All the 98 children attained morphologic remission at the end of induction. All children with hyperdiploidy (7/7) attained remission and MRD negativity, but one expired during maintenance chemotherapy of disseminated tuberculosis. The child with hypodiploidy was MRD-positive. Three (25%) children with t (12;21) were MRD-positive. All children with Ph + ALL, t(1:19), and t(4;11) were MRD-negative. Fifty-two children had no detected abnormalities, six of whom had MRD positivity (11.5%). Conclusion  Cytogenetic and molecular genetic subgrouping prognosticates ALL outcomes. Although 25% of TEL-AML + children had MRD positivity, larger studies are required to validate the same. End-of-induction MRD outcomes did not correlate with chromosomal aberrations.