Race-specific genetic aberrations in B-acute lymphoblastic leukemia in children.

Abstract

e22000 Background: B-Acute Lymphoblastic Leukemia (B-ALL) is the most common childhood cancer and the leading cause of death in children. Studies have shown that African-American (AA) children have significantly lower survival rates compared to European-American (EA) children. This disparity is not related to socioeconomic variables, suggesting a molecular basis for the lower survival. Here we present a study showing genetic aberrations (GA) involved in race-specific leukemogenesis and contribute to health disparities in B-ALL in AA and EA children. Methods: A total of 20 newly diagnosed pediatric patients were studied (5 AA and 15 EA) at University of Mississippi Medical Center. Ages range between 1 and 18 years with a median age of 4 years. None of the patients in our study had a relapse. Frozen bone marrow (BM) aspirates were used to extract DNA and whole-exome DNA sequencing was performed, focusing on race and B-ALL specific germ-line mutations. Results: Most GA were shared between AA and EA, for example those present in the Anaplastic Lymphoma Receptor Tyrosine Kinase (ALK) gene. Some genes with GA were specific to AA and others to EA. Genetic non-synonymous germ-line aberrations were identified such as, Lipoma Preferred Partner Gene, in AA and Leukemia Inhibitory Factor Receptor, in EA. Ingenuity pathway analysis revealed these genes clustered in race-specific canonical pathways. In AA, the pathways were related to telomerase signaling and cancer signaling. While in EA, it was related to stem cell pluripotency and hereditary cancer. Conclusions: The prevalence of GA in B-ALL may contribute to differences in outcomes between AA and EA children. Aberrant biological networks revealed by our study, will provide information on distinguishing signaling networks involved in race-specific leukemogenesis. Our study provides a strong basis to develop a race-specific prognostic assay for B-ALL in BM aspirates. In the future, this can help guide risk stratification and treatments based on race and advance the prognostication of B-ALL in AA children. Funding: Hyundai Hope on Wheels Scholar Grant, UMMC Division of Pediatric Hematology Oncology.