Genetic Mutations in B-Acute Lymphoblastic Leukemia Among African American and European American Children

Abstract

Background: The survival of patients with B-acute lymphoblastic leukemia (B-ALL) is significantly lower in African American (AA) children compared with European American children (EA). Here, we present a whole exome sequencing (WES) study showing race-specific genetic variations that may play a role on the disparate outcomes among AA and EA children with B-ALL.

Patients and methods: Five AA and 15 EA patients ranging in age from 1 to 18 years were enrolled. The median blast percentage was 94.8% (range, 64.5%-99.9%). Frozen bone marrow aspirate was used to extract DNA, and WES was performed, focusing on race and B-ALL-specific germline mutations.

Results: Most genetic variants (n = 339) were shared between AA and EA children. Some genetic aberrations were only uniquely identified in AA (n = 58) and others in EA (n = 52) In AA, the genetic aberrations clustered in canonical pathways related to telomerase signaling and cancer signaling. In EA, the unique genetic aberration clustered in pathways related to stem cell pluripotency and hereditary cancer.

Conclusions: Our study revealed aberrant genetic aberrations in signaling networks that may contribute to race-specific aspects of leukemogenesis. Our results suggest the value of WES as a tool for development of individual gene signatures and gene scores for AA and EA children afflicted by B-ALL. These findings may ultimately impact disease management and contribute to the elimination of disparate outcomes in AA children with B-ALL.

Keywords: B-ALL; Genetic aberrations; Pediatric; Race; Whole exome sequencing.