Transcriptional regulators and myelopoiesis: the role of serum response factor and CREB as targets of cytokine signaling.

Hematopoiesis is a complex process in which mature myeloid and lymphoid cells are produced from a small population of pluripotent stem cells within the bone marrow. Blood cell formation occurs, in part, by progenitor cell exposure to humoral growth regulators, known as hematopoietic cytokines, as well as by the regulated expression of genes by transcription factors. In this paper, we review two important nuclear proteins, the serum response factor and the cyclic adenosine monophosphate response element-binding protein, as downstream targets of mitogens, with a specific focus on hematopoietic cytokine signaling and the role these proteins play in gene regulation.

Expression of cyclic adenosine monophosphate response-element binding protein in acute leukemia.

Cyclic adenosine monophosphate response-element binding protein (CREB) is a nuclear protein that regulates expression of genes that control cell proliferation, differentiation, and survival. To analyze CREB expression in leukemia cells, we conducted Western blot analysis of bone marrow cells obtained from patients with acute lymphoblastic leukemia, patients with acute myeloid leukemia, and patients without active leukemia. CREB was expressed at a higher frequency in bone marrow cells from patients with acute lymphoid or myeloid leukemia than in patients with leukemia remission or without leukemia. Our results indicate that CREB expression could be a useful marker for leukemia in patients with acute disease and suggest a role for CREB in leukemogenesis.