Copyright © 2005 Cell Press. All rights reserved.
Cancer Cell, Vol 7, 351-362, April 2005
Article
The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia
1 Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Mattel Children’s Hospital, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90095
2 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095
3 Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095
4 Molecular Biology Institute, UCLA, Los Angeles, California 90095
5 Division of Biology, California Institute of Technology, Pasadena, California 91125
*Corresponding author
Kathleen M. Sakamoto
kms@ucla.edu
Summary
CREB is a transcription factor that functions in glucose homeostasis, growth factor-dependent cell survival, and memory. In this study, we describe a role of CREB in human cancer. CREB overexpression is associated with increased risk of relapse and decreased event-free survival. CREB levels are elevated in blast cells from patients with acute myeloid leukemia. To understand the role of CREB in leukemogenesis, we studied the biological consequences of CREB overexpression in primary human leukemia cells, leukemia cell lines, and transgenic mice. Our results demonstrate that CREB promotes abnormal proliferation and survival of myeloid cells in vitro and in vivo through upregulation of specific target genes. Thus, we report that CREB is implicated in myeloid cell transformation.
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