Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
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 ma...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54443-3 |
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| author | Yun Soo Hong Sergiu Pasca Wen Shi Daniela Puiu Nicole J. Lake Monkol Lek Meng Ru Megan L. Grove Anna Prizment Corinne E. Joshu Elizabeth A. Platz Eliseo Guallar Dan E. Arking Lukasz P. Gondek |
| author_facet | Yun Soo Hong Sergiu Pasca Wen Shi Daniela Puiu Nicole J. Lake Monkol Lek Meng Ru Megan L. Grove Anna Prizment Corinne E. Joshu Elizabeth A. Platz Eliseo Guallar Dan E. Arking Lukasz P. Gondek |
| author_sort | Yun Soo Hong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7f8586a4638e405dbde112e6a26b0a05 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7f8586a4638e405dbde112e6a26b0a052024-11-24T12:33:07ZengNature PortfolioNature Communications2041-17232024-11-0115111510.1038/s41467-024-54443-3Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasmsYun Soo Hong0Sergiu Pasca1Wen Shi2Daniela Puiu3Nicole J. Lake4Monkol Lek5Meng Ru6Megan L. Grove7Anna Prizment8Corinne E. Joshu9Elizabeth A. Platz10Eliseo Guallar11Dan E. Arking12Lukasz P. Gondek13McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of MedicineDivision of Hematological Malignancies, Johns Hopkins University School of MedicineMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of MedicineDepartment of Biomedical Engineering, Johns Hopkins UniversityDepartment of Genetics, Yale School of MedicineDepartment of Genetics, Yale School of MedicineDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public HealthHuman Genetics Center; Department of Epidemiology, Human Genetics, and Environmental Sciences; School of Public Health, The University of Texas Health Science Center at HoustonDepartment of Laboratory Medicine & Pathology, University of Minnesota Medical SchoolSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineDepartment of Epidemiology, School of Global Public Health, New York UniversityMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of MedicineDivision of Hematological Malignancies, Johns Hopkins University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-024-54443-3 |
| spellingShingle | Yun Soo Hong Sergiu Pasca Wen Shi Daniela Puiu Nicole J. Lake Monkol Lek Meng Ru Megan L. Grove Anna Prizment Corinne E. Joshu Elizabeth A. Platz Eliseo Guallar Dan E. Arking Lukasz P. Gondek Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms Nature Communications |
| title | Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| title_full | Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| title_fullStr | Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| title_full_unstemmed | Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| title_short | Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| title_sort | mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms |
| url | https://doi.org/10.1038/s41467-024-54443-3 |
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