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Gender‐related differences in the outcomes and genomic landscape of patients with myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes
Author(s) -
Karantanos Theodoros,
Gondek Lukasz P.,
Varadhan Ravi,
Moliterno Alison R.,
DeZern Amy E.,
Jones Richard J.,
Jain Tania
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17534
Subject(s) - medicine , myeloproliferative neoplasm , hazard ratio , myelodysplastic syndromes , international prognostic scoring system , neuroblastoma ras viral oncogene homolog , oncology , myelofibrosis , odds ratio , myeloid , confidence interval , gastroenterology , immunology , cancer , bone marrow , kras , colorectal cancer
Summary Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes show a male predominance and men with MDS/MPN have worse outcomes, but it is unknown if the mutational burden differs between genders. We reviewed 167 patients with MDS/MPN and found that men had worse overall survival [hazard ratio (HR) 2·09, 95% confidence interval (CI) 1·16–3·75; P = 0·013] independent of subtype, Revised International Prognostic Scoring System score and age at diagnosis. We analysed the genomic data of a subset of 100 patients. Men had 0·88 more somatic mutations on average (95% CI 0·20–1·56, P = 0·011) independent of subtype, sample source and blast percentage. More somatic mutations was associated with a higher incidence of transformation to acute myeloid leukaemia (subdistribution HR 1·30, 95% CI 1·01–1·70; P = 0·046). Men had 0·70 more mutations in high‐risk genes [additional sex combs like‐1 ( ASXL1 ), enhancer of zeste homolog 2 ( EZH2 ), Runt‐related transcription factor 1 ( RUNX1 ), SET binding protein 1 ( SETBP1 ), NRAS proto‐oncogene, GTPase ( NRAS ), stromal antigen 2 ( STAG2 )] on average (95% CI 0·11–1·29, P = 0·021), and 13‐times higher odds of harbouring an EZH2 mutation (95% CI 1·64–102·94, P = 0·015). The presence of an EZH2 mutation was associated with worse survival among men (HR 2·98, 95% CI 1·1–8·0; P = 0·031). Our present findings suggest that the worse outcomes in men with MDS/MPN are associated with a higher number of somatic mutations, especially in high‐risk genes. These results warrant validation in larger cohorts and investigation of the underlying mechanisms.