Prognostic mutations identified by whole-exome sequencing and validation of the Molecular International Prognostic Scoring System in myelodysplastic syndromes after allogeneic haematopoietic stem cell transplantation.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE

Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications

Myelodysplastic Syndromes*/genetics ; Myelodysplastic Syndromes*/therapy ; Myelodysplastic Syndromes*/mortality ; Hematopoietic Stem Cell Transplantation* ; Mutation* ; Exome Sequencing* ; Nucleophosmin*; Humans ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Aged ; Adolescent ; Young Adult ; Transplantation, Homologous

In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.
(© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

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2021ZKQA01 Translational Research Grant of NCRCH; 81100342 National Natural Science Foundation of China; 81873432 National Natural Science Foundation of China; 82070143 National Natural Science Foundation of China; 82230005 National Natural Science Foundation of China; 82200133 National Natural Science Foundation of China; BE2021645 Grants from the Jiangsu Province of China; Priority Academic Program Development of Jiangsu Higher Education Institutions

Keywords: Molecular International Prognostic Scoring System; haematopoietic stem cell transplantation; myelodysplastic syndrome; prognosis; whole‐exome sequencing

117896-08-9 (Nucleophosmin)
0 (NPM1 protein, human)

Date Created: 20240813 Date Completed: 20241116 Latest Revision: 20241116

20241118

10.1111/bjh.19707

39138006