Farnesyl Transferase Inhibitors Targeting The Treatment Of Myeloid Leukemia Effects And Mechanisms

Objective To investigate the expression and pathophysiological significance of extracellular signal-regulated kinase (ERK) / mitogen- activated protein kinase (MAPK) in myeloid leukemia. Methods Myeloid leukemia cell lines HL-60, K562 cells, bone marrow mononuclear cells (BMMNCs) from 31 acute myeloid leukemia (AML)patients at diagnosis, 21 chronic myeloid leukemia (CML) patients at diagnosis and 14 AML patients in complete remission (CR) were examined. The expression levels of phospho-ERK1/2 (phospho-P44/42MAPK) and ERK2 (P42MAPK) were detected by flow cytometry and Western blot. Results There were no difference in the expression levels of phospho-ERK1/2 (phospho-P44/42MAPK) and ERK2 (P42MAPK) between normal BMMNCs and AML-CR BMMNCs. The expression levels of phospho-ERK1/2(phospho-P44/42MAPK) and ERK2 (P42MAPK) in HL-60 cells and BMMNCs from AML patients at diagnosis were significantly higher than those in BMMNCs from AML-CR and normal donors (P<0.05). The expression levels of phospho-ERK1/2 and ERK2 in K562 cells and BMMNCs from CML patients at diagnosis were also significantly higher than those in normal cells(P<0.05). Flow cytometry showed that ratios of phospho-ERK1/2 hyperexpression in AML and CML patients at diagnosis were 80.6%(25/31) and 61.9% (13/21) respectively. Western blot also indicated that ratios of both phospho-ERK1/2 (phospho-P44/42MAPK) and ERK2 (P42MAPK) hyperexpression in AML and CML patients at diagnosis were 77.4%(24/31) and 52.4%(11/21) respectively. Conclusion Constitutive ERK/MAPK phosphorylation was observed in most patients with myeloid leukemia. Constitutive activation of ERK/MAPK signaling pathway plays an important role in the pathogenesis of myeloid leukemia.