JCI - Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia

Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia

Michele Milella, Steven M. Kornblau, Zeev Estrov, Bing Z. Carter, Hélène Lapillonne, David Harris, Marina Konopleva, Shourong Zhao, Elihu Estey, Michael Andreeff

Published in Volume 108, Issue 6

J Clin Invest. 2001; 108(6):851–859 doi:10.1172/JCI12807

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Figure 4

MEK inhibition downregulates antiapoptotic proteins of the IAP and Bcl-2 families. (a) OCI-AML3, HL-60, and U937 cells were cultured under standard conditions for 48 hours in the presence of DMSO or PD98059 (20 μM), and then subjected to Western blot analysis with Ab’s specific for the indicated antiapoptotic proteins of IAP (survivin, XIAP) and Bcl-2 (Mcl-1, Bcl-X_L, Bcl-2) families. Results are representative of one of three independent experiments. (b) The MAPK phosphorylation status of AML cell lines was assessed by Western blot analysis. The ratio of phosphorylated to total p42^MAPK (Phospho/total p42^MAPK) was then plotted against the percent reduction in survivin expression observed in the corresponding cell lines after PD98059 treatment, and regression analysis was performed (R² = 0.9104, P = 0.012). Results are representative of one of three independent experiments.