Abstract
Recognition of the importance of germline predisposition to hematopoietic malignancies, especially to the myeloid malignancies, is increasing with dramatic expansion in the number of involved genes. Diagnosis of germline predisposition has important implications for the clinical management of patients, choice of allogeneic stem cell donor, and surveillance strategies for patients and their relatives who share the deleterious variant. We now understand that there is extensive overlap in genes that confer risk for myeloid malignancies with those that confer risk for lymphoid malignancies, immunodeficiencies, and solid tumors, with more intersections likely to be uncovered in the future. Germline genetic testing should be considered standard of care now for anyone aged 40 or younger diagnosed with myelodysplastic syndrome given the high likelihood of identifying a deleterious variant. The increasing use of molecular profiling of malignant cells provides an opportunity to identify individuals without striking personal and/or family histories of cancer given how often predisposition genes are mutated somatically in these diseases and are therefore included on gene panels. The future will likely bring the identification of more risk genes, recognition of factors that promote leukemia development and development of diagnostic and surveillance guidelines for germline mutation carriers.
Original language | English (US) |
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Title of host publication | Pathogenesis and Treatment of Leukemia |
Publisher | Springer Nature |
Pages | 395-404 |
Number of pages | 10 |
ISBN (Electronic) | 9789819938100 |
ISBN (Print) | 9789819938094 |
DOIs | |
State | Published - Jan 1 2023 |
Keywords
- Deleterious variant
- Germline DNA
- Germline predisposition
- Inherited cancer
- Myeloid malignancy
ASJC Scopus subject areas
- General Medicine