The role of IRF1 and IRF2 transcription factors in leukaemogenesis.
Acute myeloid leukaemia (AML) is the most common form of leukaemia in adults. Although of the order of 75-85% of patients will achieve complete remission after induction chemotherapy, long-term survival is still relatively low. Despite the progress in the rational design of drugs in disorders such as chronic myeloid leukaemia, AML lacks a single specific pathogenomic event to act as a drug target. Interferon regulatory factor 1 (IRF1) is a member of a family of related proteins that act as transcriptional activators or repressors. IRF1 and its functional antagonist IRF2 originally discovered as transcription factors regulating the interferon-beta (IFN-beta) gene, are involved in the regulation of normal haematopoiesis and leukaemogenesis. IRF1 appears to act as a tumour suppressor gene and IRF2 as an oncogene. IRF1 acts to repress IRF2 function through the repression of cyclin-dependent kinase (CDK) inhibitor p21WAF1 critical for cell growth control. It appears that the tumour suppression function of IRF1 is abolished by IRF2. This review focuses on the interaction between IRF1 and IRF2 in myeloid development and leukaemogenesis, particularly in relation to the Ras signalling pathway. IRF2 may be a viable and specific therapeutic target in human leukaemia.
Choo
Ailyn
A
Children's Cancer Institute Australia for Medical Research, Randwick, Sydney, Australia.
Palladinetti
Patricia
P
Passioura
Toby
T
Shen
Sylvie
S
Lock
Richard
R
Symonds
Geoff
G
Dolnikov
Alla
A
D000208:Acute Disease; D000818:Animals; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000502:physiology*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000502:physiology*; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D023421:Models, Animal; D010641:Phenotype; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D018631:ras Proteins