Molecular mechanisms of cellular proliferation in acute myelogenous leukemia by leptin

Abstract

Leptin acts as a growth factor in normal cells as well as in various types of cancer cells. We investigated the effects of leptin on human acute myelogenous leukemia (AML) cells. Lewin stimulated the proliferation of HEL cells through the phosphorylation of STAT3 and ERK1/2. The blocking of STAT3 phosphorylation with the specific inhibitor. AG490, significantly reduced leptin-induced ERK1/2 phosphorylation and cellular proliferation, whereas the blocking of ERK1/2 activation by the specific ERK1/2 inhibitor, PD98059, did not affect the STAT3 phosphorylation or leptin-induced proliferation in HEL cells. Furthermore, knockdown of leptin receptor (OB-R) expression with stealth RNA interference (RNAi) reduced the leptin-induced proliferation of HEL cells and also significantly attenuated leptin-induced STAT3 and ERK1/2 activation. These results suggest that leptin promotes AML cell growth by activating STAT3 and MAPK, although not directly dependent on ERK.