Alterations in IRF1/IRF2 expression in acute myelogenous leukemia.
The interferon response genes 1 and 2 have been shown to be involved in the regulation of differentiation and proliferation of cells of the myeloid series, with the former functioning as an anti-oncogene and the latter as an oncogene. In the study described here, the levels of expression of these two genes and the ratio of their expression were compared in AML and normal marrow. The ratio of gene expression was significantly less in AML marrow cells as compared to normal marrow cells [med ratio = 1.33 vs. 2.97, P = 0.003]. While the expression ratio was unaffected by the presence or absence of either ras or fms mutations, p53 mutations were associated with higher IRF1:IRF2 expression ratios that wt p53 genes [med = 1.701 vs. 1.135, P = 0.014]. Given the functional characteristics and the competitive nature of these two genes, it is possible that leukemic transformation is associated with a fall in IRF1:IRF2 ratios. Finally, the administration of IL4 can result in the normalization of the IRF1:IRF2 ratio in the marrow cells of some patients with AML.
Preisler
H D
HD
Rush Cancer Institute, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA. hpreisler@rush.edu
Perambakam
S
S
Li
B
B
Hsu
W T
WT
Venugopal
P
P
Creech
S
S
Sivaraman
S
S
Tanaka
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D015847:Interleukin-4 / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D012016:Reference Values; D012097:Repressor Proteins; D014157:Transcription Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D015847:Interleukin-4; D016186:Receptor, Macrophage Colony-Stimulating Factor