Germline Predisposition to Myeloid Neoplasms: Diagnostic Concepts and Classifications

Molecular and sequencing advances have led to substantial breakthroughs in the discovery of new genes and inherited mutations associated with increased risk of developing myeloid malignancies. Many of the same germline mutated genes are also drivers of malignancy in sporadic cancer. Recognition of myeloid malignancy associated with germline mutations is essential for proper therapy, disease surveillance, informing related donor selection for hematopoietic stem cell transplantation, and genetic counseling of the patient and affected family members. Some germline mutations are associated with syndromic features that precede the development of malignancy; however, penetrance may be highly variable leading to masking of the syndromic phenotype and/or inherited etiology.