The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis

Yasuhiko Kamikubo, R. Katherine Hyde, Ling Zhao, Lemlem Alemu, Cecilia Rivas, Lisa J. Garrett, P. Paul Liu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The C-terminus of CBFβ-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for selfmultimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFβ-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFβ-SMMHC (CBFβ-SMMHCδC95). Embryos with a single copy of CBFβ-SMMHCδC95 were viable and showed no defects in hematopoiesis, whereas embryos homozygous for the CBFβ-SMMHCδC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFβ-SMMHC. Importantly, unlike mice expressing full-length CBFβ-SMMHC, none of the mice expressing CBFβ-SMMHCδC95 developed leukemia, even after treatment with a mutagen, although some of the older mice developed a nontransplantable myeloproliferative disease. Our data indicate that the CBFβ-SMMHC's C-terminus is essential to induce embryonic hematopoietic defects and leukemogenesis.

Original languageEnglish (US)
Pages (from-to)638-642
Number of pages5
JournalBlood
Volume121
Issue number4
DOIs
StatePublished - Jan 24 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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