Inherited GATA3 genetic Variants Are Associated With Childhood BCR-ABL1-Like Acute Lymphoblastic Leukemia and Increased Risk Of Relapse

摘要: Recent genomic profiling of acute lymphoblastic leukemia (ALL) has identified a novel high-risk subtype with a gene expression signature similar to that of BCR-ABL1-positive (Ph+) ALL and a poor prognosis. This novel BCR-ABL1-like ALL subtype is characterized by genomic aberrations targeting lymphoid development, cytokine receptor, and tyrosine kinase signaling pathways, e.g., IKZF1 deletion, CRLF2 rearrangements, and JAK mutations. However, the role of the inherited genetic variation in the pathogenesis of BCR-ABL1-like ALL remains unknown. Taking a genome-wide association study (GWAS) approach, we sought to examine germline single-nucleotide polymorphisms (SNPs) for their association with the predisposition to BCR-ABL1-like ALL. In the discovery GWAS, we compared germline SNP genotype frequencies between ALL cases with (N=75) vs. without (N=436) the BCR-ABL1-like …