Table of Contents Author Guidelines Submit a Manuscript
Advances in Hematology
Volume 2009 (2009), Article ID 634292, 8 pages
Review Article

CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis

1Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Molecular Biology Institute, CA Nanosystems Institute, UCLA, Los Angeles, CA 90095, USA
2Department of Pediatrics, Laboratory of Pediatric Onco-hematology, University of Padova, 35128 Padova, Italy

Received 27 February 2009; Accepted 30 May 2009

Academic Editor: Estella M. Matutes

Copyright © 2009 Salemiz Sandoval et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The cAMP response element-binding protein (CREB) is a nuclear transcription factor downstream of cell surface receptors and mitogens that is critical for normal and neoplastic hematopoiesis. Previous work from our laboratory demonstrated that a majority of patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) overexpress CREB in the bone marrow. To understand the role of CREB in leukemogenesis, we examined the biological effect of CREB overexpression on primary leukemia cells, leukemia cell lines, and CREB overexpressing transgenic mice. Our results demonstrated that CREB overexpression leads to an increase in cellular proliferation and survival. Furthermore, CREB transgenic mice develop a myeloproliferative disorder with aberrant myelopoiesis in both the bone marrow and spleen. Additional research from other groups has shown that the expression of the cAMP early inducible repressor (ICER), a CREB repressor, is also deregulated in leukemias. And, miR-34b, a microRNA that negative regulates CREB expression, is expressed at lower levels in myeloid leukemia cell lines compared to that of healthy bone marrow. Taken together, these data suggest that CREB plays a role in cellular transformation. The data also suggest that CREB-specific signaling pathways could possibly serve as potential targets for therapeutic intervention.