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 journalArticle

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Abstract

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
JournalLeukemia
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Stem Cells
Leukemia, Myeloid, Chronic Phase
Bone Marrow Cells
Hematopoietic Stem Cells
Oncogene Proteins
Myeloid Cells
Emergencies
Bone Marrow
Cell Line

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Hayashi, Y., Hirai, H., Kamio, N., Yao, H., Yoshioka, S., Miura, Y., ... Maekawa, T. (2013). C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. Leukemia, 27(3), 619-628. https://doi.org/10.1038/leu.2012.258

C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. / Hayashi, Y.; Hirai, H.; Kamio, N.; Yao, H.; Yoshioka, S.; Miura, Y.; Ashihara, E.; Fujiyama, Y.; Tenen, D. G.; Maekawa, T.

In: Leukemia, Vol. 27, No. 3, 01.03.2013, p. 619-628.

Research output: Contribution to journalArticle

Hayashi, Y, Hirai, H, Kamio, N, Yao, H, Yoshioka, S, Miura, Y, Ashihara, E, Fujiyama, Y, Tenen, DG & Maekawa, T 2013, 'C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion', Leukemia, vol. 27, no. 3, pp. 619-628. https://doi.org/10.1038/leu.2012.258
Hayashi, Y. ; Hirai, H. ; Kamio, N. ; Yao, H. ; Yoshioka, S. ; Miura, Y. ; Ashihara, E. ; Fujiyama, Y. ; Tenen, D. G. ; Maekawa, T. / C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. In: Leukemia. 2013 ; Vol. 27, No. 3. pp. 619-628.
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