Constitutive activation of P38 mapk, but not nf-κb, in leukemia cells from patients with acute myeloid leukemia

Abstract

Abstract Activation of p38 MAPK and NF-κB plays a role in cell proliferation. We found that constitutive activation of both NF-κB and p38 MAPK is critical for survival and proliferation of the Hut-78 lymphoma cell line and the activation of NF-κB and p38 MAPK was observed in TNF-α-treated leukemia cell lines including Mo7e and HEL cell lines. We and others also reported that activation of p38 MAPK was required for expression of NF-κB-driven genes. To determine the role of constitutively activation of these molecules in survival of leukemia cells, we analyzed the activation and relationship of p38, p44/p42 and NF-κB signaling molecules in primary leukemia cells from bone marrow or peripheral blood of patients with acute myeloid leukemia (AML). When phosphorylation of p38 and p44/p42 was analyzed by Western blotting, constitutive phosphorylation of p38 MAPK was detected in 11 of 22 (50%) AML patients, but only 1 of 22 samples showed slight p42 MAPK phosphorylation. When anti-p65 NF-κB antibody was used in Western blotting to examine activation in terms of the nuclear accumulation of p65 NF-κB, the results showed that only 3 of 22 samples had slight accumulation of nuclear p65 NF-κB. There is no significant correlation of the activation of p38 MAPK, p44/p42 MAPK and nuclear accumulation of p65 NF-κB in these primary AML cells. Although a high percentage of these primary AML cells showed constitutively activated p38 MAPK, the cells from only five of 22 primary AML cells survived in culture for more than 2–3 weeks. Among them, two samples had the constitutively activated p38 MAPK. Thus, our data indicated that (1) there is a differential pattern of the activation of p38, P44/p42 and NF-κB molecules in primary AML cells; (2) there is no correlation of activation among these signaling molecules, and p38 MAPK activation is not depended on the activation of either p44/p42 MAPK or NF-κB; (3) the mechanisms resulting in p38 MAPK activation in AML cells is unclear; and (4) constitutive activation of p38, p44/p42 MAPK, and NFκB had no obvious role, but themselves, in promoting growth of AML cells in culture.