Role of Germline Predisposition to Therapy-Related Myeloid Neoplasms

AbstractPurpose of ReviewTherapy-related myeloid neoplasms (t-MNs) are aggressive leukemias that develop following exposure to DNA-damaging agents. A subset of patients developing t-MN may have an inherited susceptibility to develop myeloid neoplasia. Herein, we review studies reporting t-MN and their association with a germline or inherited predisposition.Recent FindingsEmerging evidence suggests that development of t-MN is the result of complex interactions including generation of somatic variants in hematopoietic stem cells and/or clonal selection pressure exerted by the DNA-damaging agents, and immune evasion on top of any inherited genetic susceptibility. Conventionally, alkylating agents, topoisomerase inhibitors, and radiation have been associated with t-MN. Recently, newer modalities including poly (ADP-ribose) polymerase inhibitors (PARPi) and peptide receptor radionucleotide therapy (PRRT) are associated with t-MN. At the same time, the role of pathogenic germline variants (PGVs) in genes such asBRCA1/2,BARD1, orTP53 on the risk of t-MN is being explored. Moreover, studies have shown that while cytotoxic therapy increases the risk of developing myeloid neoplasia, it may be exposing the vulnerability of an underlying germline predisposition.Summaryt-MN remains a disease with poor prognosis. Studies are needed to better define an individual ’s inherited neoplastic susceptibility which will help predict the risk of myeloid neoplasia in the future. Understanding the g...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research