C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion

Y. Hayashi, H. Hirai, N. Kamio, H. Yao, S. Yoshioka, Y. Miura, E. Ashihara, Y. Fujiyama, D. G. Tenen, T. Maekawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


The BCR-ABL fusion oncoprotein accelerates differentiation and proliferation of myeloid cells during the chronic phase of chronic myeloid leukemia (CP-CML). Here, the role of CCAAT/enhancer binding protein β (C/EBPβ), a regulator for 'emergency granulopoiesis,' in the pathogenesis of CP-CML was examined. C/EBPβ expression was upregulated in Lineage-CD34+ CD38-hematopoietic stem cells (HSCs) and myeloid progenitors isolated from bone marrow of patients with CP-CML. In EML cells, a mouse HSC line, BCR-ABL upregulated C/EBPβ, at least in part, through the activation of STAT5. Myeloid differentiation and proliferation induced by BCR-ABL was significantly impaired in C/EBPβ-deficient bone marrow cells in vitro. Mice that were transplanted with BCR-ABL-transduced C/EBPβ knockout bone marrow cells survived longer than mice that received BCR-ABL-transduced wild-type (WT) bone marrow cells. Significantly higher levels of leukemic stem cells were maintained in BCR-ABL-transduced C/EBPβ-deficient cells than in BCR-ABL-transduced WT cells. These results suggest that C/EBPβ is involved in BCR-ABL-mediated myeloid expansion. Further elucidation of the molecular mechanisms underlying the C/EBPβ-mediated stem cell loss might reveal a novel therapeutic strategy for eradication of CML stem cells.

Original languageEnglish
Pages (from-to)619-628
Number of pages10
Issue number3
Publication statusPublished - 03-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research


Dive into the research topics of 'C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion'. Together they form a unique fingerprint.

Cite this