Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11

Ricia K Hyde, Yasuhiko Kamikubo, Stacie Anderson, Martha Kirby, Lemlem Alemu, Ling Zhao, P. Paul Liu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. Here we show that Cbfb-MYH11 caused Cbfb/Runx1 repression-independent defects in both primitive and definitive hematopoiesis. During primitive hematopoiesis, Cbfb-MYH11 delayed differentiation characterized by sustained expression of Gata2, Il1rl1, and Csf2rb, a phenotype not found in Cbfb and Runx1 knockout mice. Expression of Cbfb-MYH11 in the bone marrow induced the accumulation of abnormal progenitor-like cells expressing Csf2rb in preleukemic mice. The expression of all 3 genes was detected in most human and murine CBFB-MYH11+ leukemia samples. Interestingly, Cbfb-MYH11 + preleukemic progenitors and leukemia-initiating cells did not express Csf2rb, although the majority of leukemia cells in our Cbfb-MYH11 knockin mice were Csf2rb+. Therefore Csf2rb can be used as a negative selection marker to enrich preleukemic progenitor cells and leukemia-initiating cells from Cbfb-MYH11 mice. These results suggest that Cbfb/Runx1 repression-independent activities contribute to leukemogenesis by Cbfb-MYH11.

Original languageEnglish (US)
Pages (from-to)1433-1443
Number of pages11
JournalBlood
Volume115
Issue number7
DOIs
StatePublished - Feb 18 2010

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Leukemia
Genes
Hematopoiesis
Chromosomes
Bone
Fusion reactions
Stem Cells
Cells
Chromosomes, Human, Pair 16
Defects
Gene Fusion
Acute Myeloid Leukemia
Knockout Mice
Bone Marrow
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11. / Hyde, Ricia K; Kamikubo, Yasuhiko; Anderson, Stacie; Kirby, Martha; Alemu, Lemlem; Zhao, Ling; Liu, P. Paul.

In: Blood, Vol. 115, No. 7, 18.02.2010, p. 1433-1443.

Research output: Contribution to journalArticle

Hyde, Ricia K ; Kamikubo, Yasuhiko ; Anderson, Stacie ; Kirby, Martha ; Alemu, Lemlem ; Zhao, Ling ; Liu, P. Paul. / Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11. In: Blood. 2010 ; Vol. 115, No. 7. pp. 1433-1443.
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