Germline Variant Burden Warrants Universal Genetic Testing in Pediatric Myeloid Leukemia.

ABSTRACT: Causal germline genetic variants are frequently detected in young (under age 40) patients presenting with myelodysplastic syndromes (MDS) or bone marrow failure (BMF), where progression to acute myeloid leukemia (AML) contributes substantially to mortality in these patients. We reasoned that de novo pediatric AML, which shares clinical and biological characteristics, might also share germline genetic risk variants. We investigated germline variants in a large cohort (n=365) of pediatric AML patients with whole-genome sequencing (WGS), 29 with matched marrow-derived stromal cells, and 336 with matched remission marrow samples. Variants were deemed "likely germline" based on variant allele frequency (VAF) across available samples. Following American College of Medical Genetics and Gen

SUBMITTER: Harmon LM 

PROVIDER: S-EPMC12324642 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature