STAT-RELATED TRANSCRIPTION FACTORS ARE CONSTITUTIVELY ACTIVATED IN PERIPHERAL-BLOOD CELLS FROM ACUTE-LEUKEMIA PATIENTS

A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activ ators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with a cute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nu clear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the b eta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleo tide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioa ctive oligonucleotides as competitors to show the specificity of the c omplex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments, STAT5- and STAT1-re lated factors were detected in ALL and STAT1-, STAT3-, and STAT5-relat ed proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activate d in vivo. It is likely that the constitutive activation of STAT prote ins is a part of the events of leukemogenesis. (C) 1996 by The America n Society of Hematology.