Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Author Correction: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The ASXL1-G643W variant accelerates the development of CEBPA mutant acute myeloid leukemia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Myelodysplastic syndrome patient-derived xenografts: from no options to many

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that "non-mutated" splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels.

OriginalsprogEngelsk
Artikelnummer172
TidsskriftNature Communications
Vol/bind10
Udgave nummer1
Sider (fra-til)172
ISSN2041-1723
DOI
StatusUdgivet - 11 jan. 2019

ID: 56215098