[Clinical significance of germline pathogenic variants associated with hematologic malignancies].

The onset of hematologic malignancies is influenced not only by acquired somatic mutations but also by pathogenic germline variants to a broader extent than previously assumed. Although germline predisposition was traditionally thought to be limited to inherited bone marrow failure syndromes such as Fanconi anemia or to characteristic familial cases, pathogenic variants in RUNX1, ETV6, GATA2, and DDX41 are now known to be associated with diverse hematologic malignancies, including leukemia/MDS, across a wide age range from childhood to adulthood. With the widespread use of cancer genomic profiling tests, germline findings are encountered more frequently, which has contributed to improved diagnostic accuracy, individualized treatment selection and transplant conditioning, donor selection, and evaluation of secondary cancer risk. However, careful selection and interpretation of "normal" specimens is required given the risk of tumor cell contamination in peripheral blood. This article summarizes the overall landscape and key clinical points, and outlines prospects for multidisciplinary collaboration and evidence-building.