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Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation.

While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only a limited number of transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here, we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is required for hematopoietic progenitor cell fate decisions and for early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells toward the granulocytic/macrophage lineage while reducing the numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of Mtg16 impaired the rapid expansion of short-term stem cells, multipotent progenitor cells, and megakaryocyte-erythroid progenitor cells that is required under hematopoietic stress/emergency. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16(-/-) defect.

Pubmed ID: 18710942 RIS Download

Mesh terms: Anemia | Animals | Antigens, CD34 | Bone Marrow Cells | Cell Lineage | Cell Proliferation | Chromosomes, Mammalian | Colony-Forming Units Assay | Female | Gene Deletion | Gene Regulatory Networks | Hematopoietic Stem Cells | Humans | Male | Megakaryocytes | Mice | Multipotent Stem Cells | Myeloid Progenitor Cells | Nuclear Proteins | Phenylhydrazines | Proto-Oncogene Proteins c-kit | Proto-Oncogene Proteins c-myc | Receptors, IgG | Time Factors | Transcription Factors | Translocation, Genetic

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA112005
  • Agency: NCI NIH HHS, Id: R01-CA112005
  • Agency: NCI NIH HHS, Id: T32 CA009582
  • Agency: NCI NIH HHS, Id: T32 CA009385
  • Agency: NHLBI NIH HHS, Id: R01-HL088494
  • Agency: NIDDK NIH HHS, Id: P30 DK058404
  • Agency: NCI NIH HHS, Id: T32CA009385-24
  • Agency: NCI NIH HHS, Id: P30 CA068485
  • Agency: NCI NIH HHS, Id: R01-CA64140
  • Agency: NHLBI NIH HHS, Id: R01 HL088494
  • Agency: NCI NIH HHS, Id: R01 CA064140

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