Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation
Abstract Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencin...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-023-01418-4 |
| _version_ | 1797863816123383808 |
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| author | Jing Dong Christopher Staffi Buradagunta Tao Zhang Stephen Spellman Yung-Tsi Bolon Amy E. DeZern Shahinaz M. Gadalla H. Joachim Deeg Aziz Nazha Corey Cutler Chao Cheng Raul Urrutia Paul Auer Wael Saber |
| author_facet | Jing Dong Christopher Staffi Buradagunta Tao Zhang Stephen Spellman Yung-Tsi Bolon Amy E. DeZern Shahinaz M. Gadalla H. Joachim Deeg Aziz Nazha Corey Cutler Chao Cheng Raul Urrutia Paul Auer Wael Saber |
| author_sort | Jing Dong |
| collection | DOAJ |
| description | Abstract Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters. |
| first_indexed | 2024-04-09T22:41:43Z |
| format | Article |
| id | doaj.art-895c2192249f43b6861d6c677d997fa6 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-09T22:41:43Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-895c2192249f43b6861d6c677d997fa62023-03-22T12:07:43ZengBMCJournal of Hematology & Oncology1756-87222023-03-011611610.1186/s13045-023-01418-4Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantationJing Dong0Christopher Staffi Buradagunta1Tao Zhang2Stephen Spellman3Yung-Tsi Bolon4Amy E. DeZern5Shahinaz M. Gadalla6H. Joachim Deeg7Aziz Nazha8Corey Cutler9Chao Cheng10Raul Urrutia11Paul Auer12Wael Saber13Division of Hematology and Oncology, Department of Medicine, Medical College of WisconsinDivision of Hematology and Oncology, Department of Medicine, Medical College of WisconsinCIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program®/Be The Match®CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program®/Be The Match®CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program®/Be The Match®The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins MedicineDivision of Cancer Epidemiology & Genetics, NIH-NCI Clinical Genetics BranchClinical Research Division, Fred Hutchinson Cancer Research CenterCleveland Clinic FoundationStem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer InstituteDepartment of Medicine, Baylor College of MedicineLinda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of WisconsinDivision of Biostatistics, Institute for Health & Equity, and Cancer Center, Medical College of WisconsinDivision of Hematology and Oncology, Department of Medicine, CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of WisconsinAbstract Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.https://doi.org/10.1186/s13045-023-01418-4Mitochondrial genomeAllogeneic hematopoietic stem-cell transplantationMyelodysplastic syndromesPrognosisWhole-genome sequencing |
| spellingShingle | Jing Dong Christopher Staffi Buradagunta Tao Zhang Stephen Spellman Yung-Tsi Bolon Amy E. DeZern Shahinaz M. Gadalla H. Joachim Deeg Aziz Nazha Corey Cutler Chao Cheng Raul Urrutia Paul Auer Wael Saber Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation Journal of Hematology & Oncology Mitochondrial genome Allogeneic hematopoietic stem-cell transplantation Myelodysplastic syndromes Prognosis Whole-genome sequencing |
| title | Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation |
| title_full | Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation |
| title_fullStr | Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation |
| title_full_unstemmed | Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation |
| title_short | Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation |
| title_sort | prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem cell transplantation |
| topic | Mitochondrial genome Allogeneic hematopoietic stem-cell transplantation Myelodysplastic syndromes Prognosis Whole-genome sequencing |
| url | https://doi.org/10.1186/s13045-023-01418-4 |
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