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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1182-1192. Prepublished online as a Blood First Edition Paper on November 1, 2007; DOI 10.1182/blood-2007-04-083600. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-04-083600v1 111/3/1182    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cheng, J. C. Articles by Sakamoto, K. M. Search for Related Content PubMed PubMed Citation Articles by Cheng, J. C. Articles by Sakamoto, K. M. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS CREB is a critical regulator of normal hematopoiesis and leukemogenesis Jerry C. Cheng1,2, Kentaro Kinjo1,2, Dejah R. Judelson1,2, Jenny Chang1,2, Winston S. Wu1,2, Ingrid Schmid3, Deepa B. Shankar4, Noriyuki Kasahara5, Renata Stripecke5, Ravi Bhatia6, Elliot M. Landaw7, and Kathleen M. Sakamoto1,2,5,8 1 Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Mattel Children's Hospital, Jonsson Comprehensive Cancer Center; 2 Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center; 3 UCLA Flow Cytometry Core Facility, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California at Los Angeles; 4 Discovery Biology, Jubilant Biosystems, Bangalore, India; 5 Molecular Biology Institute, University of California at Los Angeles; 6 Department of Hematopoietic Stem Cell and Leukemia Biology, City of Hope, Duarte, CA; 7 Department of Biomathematics, University of California at Los Angeles; 8 Division of Biology, California Institute of Technology, Pasadena The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. M. Sakamoto and D. A. Frank CREB in the Pathophysiology of Cancer: Implications for Targeting Transcription Factors for Cancer Therapy Clin. Cancer Res., April 15, 2009; 15(8): 2583 - 2587. [Abstract] [Full Text] [PDF] M. Pigazzi, E. Manara, E. Baron, and G. Basso miR-34b Targets Cyclic AMP-Responsive Element Binding Protein in Acute Myeloid Leukemia Cancer Res., March 15, 2009; 69(6): 2471 - 2478. [Abstract] [Full Text] [PDF]

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