CREB and leukemogenesis

Abstract

Acute myeloid leukemia (AML) is one of the most common leukemias with a 20% 5-year event-free survival in adults and 50% overall survival in children, despite aggressive chemotherapy treatment and bone marrow transplantation. The incidence and mortality rates for acute leukemia have only slightly decreased over the last 20 years, and therefore greater understanding of the molecular mechanisms associated with leukemic progression is needed. To this end, a number of transcription factors that appear to play a central role in leukemogenesis are being investigated; among them is the cAMP response element binding protein (CREB). CREB is a transcription factor that can regulate downstream targets involving in various cellular functions including cell proliferation, survival, and differentiation. In several studies, the majority of bone marrow samples from patients with acute lymphoid and myeloid leukemia demonstrate CREB overexpression. Moreover, CREB overexpression is associated with a poor outcome in AML patients. This review summarizes the role of CREB in leukemogenesis.

Figure 1. The regulation of CREB activation

A variety of extracellular stimuli can promote CREB phosphorylation and activation through different kinases. CREB can then interact with coactivators to promote the transcription of CREB responsive genes. CREB target genes have been shown to mediate effects including cellular proliferation, survival, differentiation, immune response, and hematopoiesis.