Role of CREB Protein Family Members in Human Haematological Malignancies

Cyclic AMP Response Element Binding (CREB) protein is a member of the CREB/ATF (Activating Transcription Factor) family of transcription factors playing an important role in the nuclear responses to a variety of external signals that lead to proliferation, differentiation, apoptosis and survival. Other authors’ evidences have highlighted a critical role of CREB in the regulation of normal haematopoiesis and leukemogenesis due to the interaction with target genes crucially involved in the cell cycle machinery. Recent findings of our research group have demonstrated that CREB and ATF-1 phosphorylation levels are related to a different sensitivity of T leukaemia cell clones to the cytotoxic action of TNF-related apoptosis inducing ligand (TRAIL) and that low dose radiation treatment of erythroleukaemia cells (K562) can trigger CREB activation and deliver a survival signal. Since one fundamental problem of most malignancies, including those of haematological origin, is the development of multiple mechanisms of resistance, which progressively reduce or suppress the therapeutic efficacy of anticancer treatment, the early identification of biological markers of responsiveness/unre‐ sponsiveness and the follow-up of individual response are highly desirable to adjust thera‐ peutic treatments. In light of all these considerations and of the complex molecular interactions involving CREB/ATF family members, the present chapter is aimed at revising literature focusing, in particular, on the involvement of CREB/ATF family members in leukemogenesis and lymphomagenesis, in order to gain more insight into this matter that could result useful to the treatment of leukaemia and lymphoma diseases.