PLoS ONE (Jan 2011)

Runx1 loss minimally impacts long-term hematopoietic stem cells.

  • Xiongwei Cai,
  • Justin J Gaudet,
  • James K Mangan,
  • Michael J Chen,
  • Maria Elena De Obaldia,
  • Zaw Oo,
  • Patricia Ernst,
  • Nancy A Speck

DOI
https://doi.org/10.1371/journal.pone.0028430
Journal volume & issue
Vol. 6, no. 12
p. e28430

Abstract

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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.