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

Chyla BJ, Moreno-Miralles I, Steapleton MA, Thompson MA, Bhaskara S, Engel M, Hiebert SW
Mol Cell Biol. 2008 28 (20): 6234-47

PMID: 18710942 · PMCID: PMC2577421 · DOI:10.1128/MCB.00404-08

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.

MeSH Terms (27)

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 Repressor Proteins Time Factors Transcription Factors Translocation, Genetic

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