Faculty, Staff and Student Publications
Language
English
Publication Date
11-22-2024
Journal
Nature Communications
DOI
10.1038/s41467-024-54443-3
PMID
39578475
PMCID
PMC11584845
PubMedCentral® Posted Date
11-22-2024
PubMedCentral® Full Text Version
Post-print
Abstract
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.
Keywords
Humans, Mutation, DNA, Mitochondrial, Clonal Hematopoiesis, Male, Mitochondria, Female, Middle Aged, Risk Factors, Hematologic Neoplasms, Aged, Myeloproliferative Disorders, Risk Assessment, Adult, Haematological cancer, Myelodysplastic syndrome, Predictive markers
Published Open-Access
yes
Recommended Citation
Hong, Yun Soo; Pasca, Sergiu; Shi, Wen; et al., "Mitochondrial Heteroplasmy Improves Risk Prediction for Myeloid Neoplasms" (2024). Faculty, Staff and Student Publications. 1442.
https://digitalcommons.library.tmc.edu/uthsph_docs/1442