Functional analysis of the Zinc finger E-box binding homeobox 1 (ZEB1/TCF8) gene in the multi-step leukemogenesis of adult T-cell leukemia/lymphoma

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We identified that TCF8 at 10q11.2 is a candidate tumor-suppressor gene in acute-type adult-T cell leukemia/lymphoma (ATLL). The down-regulation of TCF8 expression by genetic and epigenetic abnormalities in ATLL was associated with resistance to TGF-beta1 treatment, which is one of well-known characteristics of ATL cells. The enforced expression of TCF8 partially restored the responsiveness of ATLL cells to TGF-beta1. Furthermore, TCF8 deficient mice frequently developed invasive CD4^+ T-cell lymphomas in thymus or in ascitic fluids. These findings suggest that TCF8 may become a new therapeutic target for ATLL.