[Diagnostic approaches and clinical relevance of hereditary hematological malignancies].

Abstract

Hereditary hematological malignancies (HHM) are characterized by genetic heterogeneity, variable penetrance, and expressivity. Although individual gene involvement is rare, germline pathogenic variants are estimated to be present in at least 5-10% of hematological malignancies. In cases diagnosed at young age, with positive family history, or with multiple malignancies (including myeloid neoplasms after cytotoxic treatments), the prevalence rises, reaching 13-21%. Germline-focused tumor analysis may suggest genetic predisposition even without clinical suspicion. Using larger gene panels or whole-exome sequencing can further increase the detection rate of pathogenic germline variants to over 20%. In HHM, peripheral blood/bone marrow samples may contain somatic and germline variants. Germline confirmation requires non-hematopoietic samples, such as hair follicles or fibroblast cultures. Identifying HHM has clinical implications, especially in the timing of allogeneic stem cell transplantation, donor selection, conditioning, and follow-up. Genetic screening and counseling are essential for predisposed patients and family members to provide interdisciplinary care.