Dual role of in T-cell malignancies.

The zinc finger transcription factor B-cell CLL/lymphoma 11B gene (, ) plays a crucial role in T-cell development, but its role in T-cell malignancies has not yet been definitively clarified. In the literature, 2 contradictory hypotheses on the function of exist. One suggests that functions as tumor suppressor gene, and the other suggests that functions as oncogene. The aim of this review is to revise the current knowledge about the function of in T-cell malignancies, confront these 2 hypotheses and present a new model of dual role of in T-cell malignancies and potential new therapeutic approach, based on recent findings of the function of in DNA damage repair. Decreased expression, resulting in deficient DNA repair, may facilitate DNA mutations in rapidly proliferating T-cell progenitors that undergo gene rearrangements, thereby leading to malignant transformation. On the other hand, decreased expression and inefficient DNA repair may result in accumulation of DNA damages in genes crucial for the cell survival and in apoptosis of malignant T cells. We hypothesize that T-cell malignancies expressing high levels of might be dependent on it. In those cases, targeted inhibition of expression may have a therapeutic effect. The antitumor effect of suppression might be strengthened by generation of induced T to NK cells (ITNK). Therefore, there is an urgent need to develop a specific inhibitor.