The characterization of the role of myeloid translocation gene 16 in hematopoietic progenitor and stem cell functions
Fischer, Melissa Ann
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2011-08-25
Abstract
The t(8;21) and t(16;21) that are associated with acute myeloid leukemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8, also known as ETO) and 16 (MTG16 also known as ETO2), respectively. Although it has been shown that MTG family members bridge histone deacetylases and DNA binding transcription factors to mediate transcriptional repression, less is known about the physiological functions of this gene family. Given that many of the transcription factors that recruit Mtg16 are known regulators of hematopoiesis, we hypothesized that Mtg16 plays a key regulatory role during hematopoiesis. To test this, we created mice lacking Mtg16 to better understand the physiological action of this key regulator. Overall, deletion of Mtg16 in a murine model resulted in numerous hematopoietic defects, such as altered lineage cell fate decisions, proliferation defects of various hematopoietic cells, maintenance of genomic stability, and ultimately, loss of functional integrity of the HSCs.