Ectopic expression of the transcription factor ONECUT3 drives a complex karyotype in myelodysplastic syndromes.

ABSTRACT: Chromosomal instability is a prominent biological feature of myelodysplastic syndromes (MDS), with over 50% of patients with MDS harboring chromosomal abnormalities or a complex karyotype (CK). Despite this observation, the mechanisms underlying mitotic and chromosomal defects in MDS remain elusive. In this study, we identified ectopic expression of the transcription factor ONECUT3, which is associated with CKs and poorer survival outcomes in MDS. ONECUT3-overexpressing cell models exhibited enrichment of several notable pathways, including signatures of sister chromosome exchange separation and mitotic nuclear division with the upregulation of INCENP and CDCA8 genes. Notably, dysregulation of chromosome passenger complex (CPC) accumulation, besides the cell equator and midbody, during mit

SUBMITTER: Luo Y 

PROVIDER: S-EPMC11014670 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature