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

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Clonal diversity predicts adverse outcome in chronic lymphocytic leukemia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Distinct immune phenotypes in infants developing asthma during childhood

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Infant airway microbiota and topical immune perturbations in the origins of childhood asthma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are important downstream effectors of oncogenic fusion proteins involving the mixed lineage leukemia (MLL) gene. A well-characterized member of this protein family is MEIS1, which orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). TGIF1/TGIF2 are relatively uncharacterized TALE transcription factors, which in contrast to the remaining family, have been shown to act as transcriptional repressors. Given the general importance of this family in malignant haematopoiesis we therefore tested the potential function of TGIF1 in the maintenance of MLL-rearranged AML. Gene expression analysis of MLL-rearranged patient blasts demonstrated reduced TGIF1 levels and, in accordance, we find that forced expression of TGIF1 in MLL-AF9 transformed cells promoted differentiation and cell cycle exit in vitro, and delayed leukemic onset in vivo. Mechanistically, we show that TGIF1 interferes with a MEIS1-dependent transcriptional program by associating to MEIS1-bound regions in a competitive manner and that the MEIS1:TGIF1 ratio influence clinical outcome. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for leukemic maintenance and provide novel insights into regulatory gene expression circuitries in MLL-rearranged AML.Leukemia accepted article preview online, 28 October 2014. doi:10.1038/leu.2014.307.

OriginalsprogEngelsk
TidsskriftLeukemia
Vol/bind29
Sider (fra-til)1018-1031
ISSN0887-6924
DOI
StatusUdgivet - 2015

ID: 44680280