The Insulin-Like Growth Factor-1 Receptor Kinase Inhibitor, NVP-ADW742, Suppresses Survival and Resistance to Chemotherapy in Acute Myeloid Leukemia Cells

Deregulation of insulin like growth factor 1 receptor (IGF 1R) is closely associated with malignant transformation and tumor cell survival in various cancers We found that IGF 1R expression level in leukemia cells positively correlated with the percentage of blast in bone marrow from de novo acute myeloid leukemia (AML) patients Moreover we shoved that NVP ADW742 a novel small weight molecular inhibitor of IGF 1R could induce apoptosis in both HL-60 cell line and primary AML blasts However no significant alteration of cell cycle was observed in HL-60 cells Further studies revealed that NVP-ADW742 induced Akt dephosphorylation which might subsequently induce p38 phosphorylation and decrease antiapoptotic protein Bcl 2 expression in HL 60 cells Finally we demonstrated that NVP ADW742 could synergize with Ara C to induce the kill in a subset of drug resistant AML specimens We suggested that IGF-1R targeting might be therapeutically beneficial for some AML patients