Molecular features of early onset adult myelodysplastic syndrome
Cassandra M. Hirsch,
Bartlomiej P. Przychodzen,
Tomas Radivoyevitch,
Bhumika Patel,
Swapna Thota,
Michael J. Clemente,
Yasunobu Nagata,
Thomas LaFramboise,
Hetty E. Carraway,
Aziz Nazha,
Mikkael A. Sekeres,
Hideki Makishima,
Jaroslaw P. Maciejewski
Affiliations
Cassandra M. Hirsch
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA;Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA
Bartlomiej P. Przychodzen
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Tomas Radivoyevitch
Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, OH, USA
Bhumika Patel
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Swapna Thota
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Michael J. Clemente
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Yasunobu Nagata
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Thomas LaFramboise
Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA
Hetty E. Carraway
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Aziz Nazha
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Mikkael A. Sekeres
Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Hideki Makishima
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA;Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Japan
Jaroslaw P. Maciejewski
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA;Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA
Myelodysplastic syndromes are typically diseases of older adults. Patients in whom the onset is early may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between “early onset” patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphological subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying them based on age at presentation and clinical parameters. We then characterized molecular abnormalities detected by next-generation deep sequencing of 60 genes that are commonly mutated in myeloid malignancies. The number of mutations increased linearly with age and on average, patients >50 years of age had more mutations. TET2, SRSF2, and DNMT3A were more commonly mutated in patients >50 years old compared to patients ≤50 years old. In general, patients >50 years of age also had more mutations in spliceosomal, epigenetic modifier, and RAS gene families. Although there are age-related differences in molecular features among patients with myelodysplasia, most notably in the incidence of SRSF2 mutations, our results suggest that patients ≤50 years old belong to a disease continuum with a distinct pattern of early onset ancestral events.
