Possible involvement of aryl hydrocarbon receptor (AhR) in adult T-cell leukemia (ATL) leukemogenesis: constitutive activation of AhR in ATL

Human T-cell leukemia virus type 1 is the etiologic agent of adult T-cell leukemia (ATL), although the precise mechanism involved in the transformation process has not yet been defined. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can influence cell proliferation and differentiation. We investigated the expression and activation of AhR in ATL. RT-PCR and Western blot analyses showed high expression levels of AhR in ATL cell lines. The elevated expression of AhR was in part attributable to the action of the viral transactivator protein, Tax. Interestingly, activation of the AhR was found in ATL cell lines in the absence of apparent exogenous ligands. Importantly, the increased expression and activation of AhR were also observed in some primary ATL cells. To our best knowledge, this is the first report to show the lymphoid malignancy having constitutive activation of AhR. A possible link between increased AhR expression and leukemogenesis in ATL is discussed.