Oncogenic RAS promotes leukemic transformation of CUX1-deficient cells.

ABSTRACT: -7/del(7q) is prevalent across subtypes of myeloid neoplasms. CUX1, located on 7q22, encodes a homeodomain-containing transcription factor, and, like -7/del(7q), CUX1 inactivating mutations independently carry a poor prognosis. As with loss of 7q, CUX1 mutations often occur early in disease pathogenesis. We reported that CUX1 deficiency causes myelodysplastic syndrome in mice but was insufficient to drive acute myeloid leukemia (AML). Given the known association between -7/del(7q) and RAS pathway mutations, we mined cancer genome databases and explicitly linked CUX1 mutations with oncogenic RAS mutations. To determine if activated RAS and CUX1 deficiency promote leukemogenesis, we generated mice bearing Nras^G12D and CUX1-knockdown which developed AML, not seen in mice with eithe

SUBMITTER: An N 

PROVIDER: S-EPMC10068965 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature