Clinical, genetic, and pathologic variability in myelodysplastic syndromes and precursor conditions across race, ethnicity, and sex
Authors
Nancy Gillis, Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Christelle Colin-Leitzinger, Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Yi-Han Tang, Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Michael Otterstatter, The Emmes Company, Rockville, Maryland, USA.
Seth Sherman, The Emmes Company, Rockville, Maryland, USA.
Ling Zhang, Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Lynn C. Moscinski, Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Mary Ellen Walker, Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Jeffrey S. Painter, Tissue Core, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Gregory A. Abel, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Tareq Al Baghdadi, Department of Hematology and Oncology, Trinity Health IHA Medical Group, Michigan Cancer Research Consortium, Ypsilanti, Michigan, USA.
H Joachim Deeg, Fred Hutchinson Cancer Center, Seattle, Washington, University of Washington, Seattle, Washington, USA.
James M. Foran, Division of Hematology & Medical Oncology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida, USA.
Steven D. Gore, Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
Alexandra M. Harrington, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Steven H. Kroft, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Jane Jijun Liu, Illinois CancerCare, Heartland NCORP, Peoria, Illinois, USA.
Wael Saber, Division of Hematology/Oncology, Department of Medicine, CIBMTR Milwaukee, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Shamsuddin Virani, Advocate Health - MidwestFollow
Rafael Bejar, Division of Hematology and Oncology, UC San Diego Moores Cancer Center, La Jolla, California, USA.
R Coleman Lindsley, Department of Medical Oncology, Division of Hematological Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Eric Padron, Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Matthew J. Walter, Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Rami Komrojki, Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Amy E. DeZern, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
Mikkael A. Sekeres, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA.
Recommended Citation
Gillis N, Colin-Leitzinger C, Tang YH, et al. Clinical, Genetic, and Pathologic Variability in Myelodysplastic Syndromes and Precursor Conditions Across Race, Ethnicity, and Sex. Am J Hematol. Published online March 29, 2026. doi:10.1002/ajh.70279
Abstract
The epidemiology of myelodysplastic syndromes/neoplasms (MDS) is challenging to define due to inconsistent reporting, complex diagnostic procedures, and evolving diagnostic criteria. Using the National MDS Natural History Study-a prospective cohort with centrally adjudicated histopathology and genetic variant review-we characterized the landscape of MDS across the United States and identified differences across demographics. Among 2115 participants, 64% (1346) had an MDS spectrum condition, including MDS (24%), MDS/myeloproliferative neoplasm (5%) and precursor conditions-clonal cytopenia of undetermined significance (22%) and idiopathic cytopenia/dysplasia of undetermined significance (13%). The median age was 74 years, and participants were predominantly male (66%), White (91%), and Non-Hispanic (92%). Myeloid-associated variants were detected in 68% of participants, most commonly in TET2, DNMT3A, ASXL1, SF3B1, and SRSF2. Black, compared to White, participants were younger at diagnosis (69 vs. 74 years, p = 0.01), had equal or increased prevalence of higher-risk MDS, lower hemoglobin, and higher peripheral blood blasts, yet were less likely to receive MDS-directed therapy (14% vs. 42%, p = 0.008). Black and Hispanic participants had fewer detectable gene mutations than White participants. Females had lower variant allele frequencies and fewer RNA splicing gene mutations than males. After multivariable adjustment, TP53 mutations, MDS diagnosis, and higher-risk disease were associated with worse progression-free and overall survival; age was also associated with overall survival. Black race trended toward improved progression-free survival. These findings highlight the need for enhanced understanding of MDS pathogenesis across patient groups and refined prognostic tools to improve personalized management of MDS spectrum conditions. Trial Registration: ClinicalTrials.gov identifier: NCT02775383.
Affiliations
Aurora Health Care, Burlington