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) arises from a rare population of leukemic stem cells. Cells of this nature can initiate and maintain leukemic cell growth in both long-term cultures and nonobese 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 populations (CD34(+)/CD38(-)) were isolated and used to synthesize radiolabeled complementary DNA (cDNA). AML vs normal probes were then hybridized to cDNA arrays containing genes related to cancer and apoptosis. Of approximately 1400 genes analyzed, 2 tumor-suppressor genes were identified that were overexpressed in all 7 of the AML CD34(+)/CD38(-) cell populations: death-associated protein kinase and interferon regulatory factor 1. Expression of each gene was confirmed by reverse-transcription polymerase chain reaction and immunoblot analysis. It is proposed that tumor-suppressor proteins play a role in the biology of primitive AML cells. (Blood. 2001;97:2177-2179)
Blood and Marrow Transplant Program, Markey Cancer Center, Division of Hematology/Oncology, University of Kentucky Medical Center, Lexington, USA.
M L
ML
Guzman
D
D
Upchurch
B
B
Grimes
D S
DS
Howard
D A
DA
Rizzieri
S M
SM
Luger
G L
GL
Phillips
C T
CT
Jordan
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000208:Acute Disease; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D064550:Death-Associated Protein Kinases; D004790:Enzyme Induction; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006801:Humans; D016130:Immunophenotyping; D050856:Interferon Regulatory Factor-1; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000201:enzymology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1