Gene dosage effect of CUX1 in a murine model disrupts HSC homeostasis and controls the severity and mortality of MDS.

ABSTRACT: Monosomy 7 (-7) and del(7q) are high-risk cytogenetic abnormalities common in myeloid malignancies. We previously reported that CUX1, a homeodomain-containing transcription factor encoded on 7q22, is frequently inactivated in myeloid neoplasms, and CUX1 myeloid tumor suppressor activity is conserved from humans to Drosophila. CUX1-inactivating mutations are recurrent in clonal hematopoiesis of indeterminate potential as well as myeloid malignancies, in which they independently carry a poor prognosis. To determine the role for CUX1 in hematopoiesis, we generated 2 short hairpin RNA-based mouse models with ∼54% (Cux1^mid) or ∼12% (Cux1^low) residual CUX1 protein. Cux1^mid mice develop myelodysplastic syndrome (MDS) with anemia and trilineage dyspla

SUBMITTER: An N 

PROVIDER: S-EPMC6032890 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature