Hereditary Myelodysplastic Syndrome and Acute Myeloid Leukemia: Diagnosis, Questions, and Controversies

Purpose of Review: To review the diagnosis of individuals with hereditary hematopoietic malignancies (HHMs) that predispose to myelodysplastic syndrome and acute myeloid leukemia, barriers to HHM diagnosis, and unaddressed questions and controversies within the HHM field. Recent Findings: Pathogenic germline mutations in approximately a dozen genes predispose to HHMs, and many more genes are likely to be involved. Many of these HHM genes have only been identified recently. HHM phenotypes are diverse, but may be categorized as “purely” myeloid syndromes, syndromes with abnormal platelet number/function, and HHMs with additional organ system involvement. A number of questions remain unanswered in this emerging field, including the ideal diagnostic approach for patients at risk for HHMs, the optimal surveillance of unaffected carriers, and how to personalize care for individuals with HHMs. Summary: The field of HHMs is evolving rapidly. Ongoing research in this area will eventually inform the care of patients with both somatic and hereditary cancer syndromes, but much work remains to be done.