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Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence. | LitMetric

AI Article Synopsis

  • The t(8;21) and t(16;21) gene translocations associated with acute myeloid leukemia disrupt the closely related Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16).
  • MTG16 is essential for maintaining hematopoietic stem cell self-renewal and function, as evidenced by failed bone marrow transplant assays in Mtg16-null mice.
  • Research indicates that MTG16 suppresses key cell-cycle regulators like E2F2, and its absence leads to a higher number of long-term stem cells actively cycling, which may affect stem cell quiescence.

Article Abstract

The t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321173PMC
http://dx.doi.org/10.1038/emboj.2011.500DOI Listing

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