Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells

Cell Stem Cell. 2015 Aug 6;17(2):165-77. doi: 10.1016/j.stem.2015.06.002. Epub 2015 Jul 9.


The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating preleukemic stem cells that expand in the bone marrow. Here we show, counterintuitively, that Runx1-deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involved decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins and binds the rDNA repeats. Runx1-deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and ER stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1-deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Core Binding Factor Alpha 2 Subunit / deficiency*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Mice
  • Mutagens / toxicity
  • Organelle Biogenesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics
  • Ribosomes / drug effects
  • Ribosomes / metabolism*
  • Signal Transduction / drug effects
  • Stress, Physiological / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • Core Binding Factor Alpha 2 Subunit
  • Mutagens
  • RNA, Messenger
  • RNA, Ribosomal
  • Tumor Suppressor Protein p53
  • TOR Serine-Threonine Kinases

Associated data

  • GEO/GSE67609