Blood. 2018 Sep 5. pii: blood-2018-06-860882. doi: 10.1182/blood-2018-06-860882. [Epub ahead of print]
How I use molecular genetic tests to evaluate patients who have or may have myelodysplastic syndromes.
Abstract
Myelodysplastic syndromes (MDS) can be difficult to diagnose, especially when morphological changes in blood and marrow cells are minimal, myeloblast proportion is not increased, and the karyotype is normal. The discovery of more than 40 genes that are recurrently somatically mutated in MDS patients raised hope that molecular genetic testing for these mutations might help clarify the diagnosis in ambiguous cases where patients present with cytopenias and non-diagnostic marrow morphological findings. However, many older healthy individuals also harbor somatic mutations in leukemia-associated driver genes, especially in DNMT3A, TET2, and ASXL1 - a state termed clonal hematopoiesis of indeterminate potential (CHIP) -- and detection of common aging-associated mutations in a cytopenic patient can cause diagnostic uncertainty. Despite this potential confounding factor, certain somatic mutation patterns when observed in cytopenic patients confer a high likelihood of disease progression, and may allow a provisional diagnosis of MDS even if morphologic dysplasia and other diagnostic criteria are absent. A subset of acquired mutations also influence risk stratification of patients with an established MDS diagnosis and can inform treatment selection. Many unanswered questions remain about the implications of specific mutations, and clinicians also vary widely in their comfort with interpreting sequencing results. Here, from the standpoint of the clinical hematologist, I review the use of molecular genetic assays in patients with possible MDS or diagnosed MDS.
- PMID:
- 30185432
- DOI:
- 10.1182/blood-2018-06-860882
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