Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells

Previous studies indicate that human acute myelogenous leukemia (AML) arise s from a rare population of leukemic stem cells. Cells of this nature can i nitiate and maintain leukemic cell growth in both long-term cultures and no nobese diabetic/severe combined immune-deficient mice. To characterize the biology of primitive AML cells, gene expression screens were performed with 7 primary AML and 3 normal specimens. For each sample, stem cell populatio ns (CD34(+)/ CD38(-)) were isolated and used to synthesize radiolabeled com plementary DNA (cDNA). AML vs normal probes were then hybridized to cDNA ar rays containing genes related to cancer and apoptosis. Of approximately 140 0 genes analyzed, 2 tumor-suppressor genes were identified that were overex pressed in all 7 of the AML CD34(+)/CD38(-) cell populations: death-associa ted protein kinase and interferon regulatory factor 1. Expression of each g ene was confirmed by reverse-transcription polymerase chain reaction and im munoblot analysis. It is proposed that tumor-suppressor proteins play a rol e in the biology of primitive AML cells. (Blood. 2001;97:2177-2179) (C) 200 1 by The American Society of Hematology.