T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage

Laleh Talebian, Zhe Li, Yalin Guo, Justin Gaudet, Maren E. Speck, Daisuke Sugiyama, Prabhjot Kaur, Warren S. Pear, Ivan Maillard, Nancy A. Speck

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4-CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.

Original languageEnglish
Pages (from-to)11-21
Number of pages11
JournalBlood
Volume109
Issue number1
DOIs
Publication statusPublished - Jan 1 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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