Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network.

@article{Zaidi2009AlteredRS,
  title={Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network.},
  author={Sayyed K Zaidi and Christopher R. Dowdy and Andre J. van Wijnen and Jane B Lian and Azra Raza and Janet L Stein and Carlo Maria Croce and Gary S Stein},
  journal={Cancer research},
  year={2009},
  volume={69 21},
  pages={
          8249-55
        }
}
Disruption of Runx1/AML1 subnuclear localization, either by a single amino acid substitution or by a chromosomal translocation [e.g., t(8;21)], is linked to the etiology of acute myeloid leukemia (AML). Here, we show that this defect induces a select set of micro-RNAs (miR) in myeloid progenitor cells and AML patients with t(8;21). Both Runx1 and the t(8;21)-encoded AML1-ETO occupy the miR-24-23-27 locus and reciprocally control miR-24 transcription. miR-24 directly downregulates mitogen… Expand
An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells
TLDR
A novel regulatory circuit is established between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia. Expand
Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding
TLDR
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TLDR
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TLDR
A panel of mutations was developed to test the functions of these domains in vitro, and mouse models were developed to examine the consequences of losing Runx1 C-terminal domains on hematopoietic development and leukemogenesis in vivo. Expand
Disruption of MAPK1 expression in the ERK signalling pathway and the RUNX1‑RUNX1T1 fusion gene attenuate the differentiation and proliferation and induces the growth arrest in t(8;21) leukaemia cells.
TLDR
The current results demonstrate that MAPK1 promotes myeloid cell proliferation and differentiation simultaneously by cell cycle progression while suppresing apoptosis. Expand
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