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Title: C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion
Authors: Hayashi, Y.
Hirai, H.
Kamio, N.
Yao, H.
Yoshioka, S.
Miura, Y.
Ashihara, E.
Fujiyama, Y.
Tenen, D.G. 
Maekawa, T.
Keywords: BCR-ABL
chronic myeloid leukemia
Issue Date: Mar-2013
Citation: Hayashi, Y., Hirai, H., Kamio, N., Yao, H., Yoshioka, S., Miura, Y., Ashihara, E., Fujiyama, Y., Tenen, D.G., Maekawa, T. (2013-03). C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. Leukemia 27 (3) : 619-628. ScholarBank@NUS Repository.
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. © 2013 Macmillan Publishers Limited All rights reserved.
Source Title: Leukemia
ISSN: 08876924
DOI: 10.1038/leu.2012.258
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