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. ( IntroductionCyclic adenosine monophosphate (cAMP) response-element binding protein (CREB) is a nuclear protein that regulates gene expression on activation of cAMP-dependent or cAMP-independent signal-transduction pathways in cells. 1-3 CREB binds the cAMP response element in the promoter regions of target genes that regulate cell proliferation and survival, such as bcl-2 and egr-1. [4][5][6] Phosphorylation of CREB at serine 133 in response to growth factors modulates the function of CREB. 1,7,8 Thus, CREB was proposed to be a critical regulator of growth factor-induced gene expression leading to cell proliferation, differentiation, and survival. 1,[7][8][9][10] In studying signaling pathways activated by the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF), we previously found that CREB was phosphorylated in response to GM-CSF stimulation of myeloid leukemia cells. 6,11,12 In the current study, to determine whether CREB is overexpressed in leukemia cell lines and bone marrow specimens from patients with acute leukemia, we conducted Western blot analysis to detect the presence of CREB protein. We found that CREB was expressed in most leukemia cell lines and in bone marrow from patients with acute leukemia but that CREB levels were below the detection limit in normal bone marrow samples and in bone marrow samples from patients without active leukemia. Our results suggest that CREB could be a marker for leukemia. Study design Patient selectionWe analyzed bone marrow samples from 26 patients with newly diagnosed acute myeloid leukemia (AML), 20 patients with acute lymphoblastic leukemia (ALL), and 25 patients without active leukemia. Included in the cohort of patients without active leukemia were 9 patients with ALL and 4 patients with AML in documented remission. The nonleukemia bone marrow samples were from 4 patients with neutropenia, 4 patients with idiopathic thrombocytopenic purpura (ITP), 2 healthy volunteers (donors of bone marrow for transplantation), and 2 patients with lymphoma who underwent bone marrow aspiration as part of an evaluation for metastasis. The patients' age ranged from 4 months to 80 years. The diagnoses of leukemia were made according to standard morphologic criteria on the basis of bone marrow aspir...
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