Runx1 is required for hematopoietic defects and leukemogenesis in Cbfb-MYH11 knock-in mice

R. K. Hyde, L. Zhao, L. Alemu, P. P. Liu

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


CBFβ-SMMHC (core-binding factor β-smooth muscle myosin heavy chain), the fusion protein generated by the chromosome 16 inversion fusion gene, CBFB-MYH11, is known to initiate leukemogenesis. However, the mechanism through which CBFβ-SMMHC contributes to leukemia development is not well understood. Previously, it was proposed that CBFβ-SMMHC acts by dominantly repressing the transcription factor RUNX1 (Runt-related protein 1), but we recently showed that CBFβ-SMMHC has activities that are independent of RUNX1 repression. In addition, we showed that a modified CBFβ-SMMHC with decreased RUNX1-binding activity accelerates leukemogenesis. These results raise questions about the importance of RUNX1 in leukemogenesis by CBFβ-SMMHC. To test this, we generated mice expressing Cbfb-MYH11 in a Runx1-deficient background, resulting from either homozygous Runx1-null alleles (Runx1-/-) or a single dominant-negative Runx1 allele (Runx1 +/lz). We found that loss of Runx1 activity rescued the differentiation defects induced by Cbfb-MYH11 during primitive hematopoiesis. During definitive hematopoiesis, RUNX1 loss also significantly reduced the proliferation and differentiation defects induced by Cbfb-MYH11. Importantly, Cbfb-MYH11-induced leukemia had much longer latency in Runx1 +/lz mice than in Runx1-sufficient mice. These data indicate that Runx1 activity is critical for Cbfb-MYH11-induced hematopoietic defects and leukemogenesis.

Original languageEnglish (US)
Pages (from-to)1771-1778
Number of pages8
Issue number8
StatePublished - Aug 7 2015
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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