Role of cyclic AMP response element binding protein in human leukemias

Cancer. 2005 Nov 1;104(9):1819-24. doi: 10.1002/cncr.21401.


Acute myeloid leukemia (AML) in adults has a 20% 5-year disease-free survival despite treatment with aggressive cytotoxic chemotherapy. Previous work from our laboratory demonstrated that the majority of patients with acute lymphoid and myeloid leukemia overexpress CREB in the bone marrow. CREB overexpression is associated with poor initial outcome of clinical disease in AML patients. CREB is a transcription factor that functions in glucose homeostasis, growth-factor-dependent cell survival, and memory. Signaling by hematopoietic growth factors, such as GM-CSF, results in activation of CREB and up-regulation of CREB target genes. To study its role in hematopoiesis, we overexpressed CREB in leukemia cell lines and in mice. CREB overexpression resulted in increased survival and proliferation of myeloid cells and blast-transformation of bone marrow progenitor cells from transgenic mice expressing CREB in the myeloid lineage. CREB transgenic mice also develop myeloproliferative disease after 1 year. Thus, CREB acts as a protooncogene to regulate hematopoiesis and contributes to the leukemia phenotype. Our results suggest that CREB-dependent pathways may serve as targets for directed therapies in leukemia in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Disease-Free Survival
  • Hematopoiesis / genetics
  • Humans
  • Leukemia / genetics
  • Leukemia / metabolism*
  • Mice
  • Mice, Transgenic
  • Mutation
  • Transcription Factors / genetics
  • Up-Regulation


  • Cyclic AMP Response Element-Binding Protein
  • Transcription Factors