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Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
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Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
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Journal Article
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
2024
Overview
Clonal hematopoiesis of indeterminate potential is the primary pathogenic risk factor for myeloid neoplasms, while heteroplasmy (mutations in a subset of cellular mitochondrial DNA) is another marker of clonal expansion associated with hematological malignancies. We explore how these two markers relate and influence myeloid neoplasms incidence, and their role in risk stratification. We find that heteroplasmy is more common in individuals with clonal hematopoiesis of indeterminate potential, particularly those with higher variant allele fractions, multiple mutations, or spliceosome machinery mutations. Individuals with both markers have a higher risk of myeloid neoplasms than those with either alone. Furthermore, heteroplasmic variants with higher predicted deleteriousness increase the risk of myeloid neoplasms. Incorporating heteroplasmy in an existing risk score model for individuals with clonal hematopoiesis of indeterminate potential significantly improves sensitivity and better identifies high-risk groups. This suggests heteroplasmy as a clonal expansion marker and potentially as a biomarker for myeloid neoplasms development.
The relationship between heteroplasmy and clonal hematopoiesis of indeterminate potential and its association with the incidence of myeloid neoplasms (MN) remains to be explored. Here, the authors suggest that heteroplasmy is a marker of clonal expansion and a significant risk factor for MN development.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
