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Publication : Runx1 loss minimally impacts long-term hematopoietic stem cells.

First Author  Cai X Year  2011
Journal  PLoS One Volume  6
Issue  12 Pages  e28430
PubMed ID  22145044 Mgi Jnum  J:182271
Mgi Id  MGI:5315082 Doi  10.1371/journal.pone.0028430
Citation  Cai X, et al. (2011) Runx1 loss minimally impacts long-term hematopoietic stem cells. PLoS One 6(12):e28430
abstractText  RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs.
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