Abstract
The zinc finger transcription factor B-cell CLL/lymphoma 11B gene (BCL11B, CTIP2) 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 BCL11B exist. One suggests that BCL11B functions as tumor suppressor gene, and the other suggests that BCL11B functions as oncogene. The aim of this review is to revise the current knowledge about the function of BCL11B in T-cell malignancies, confront these 2 hypotheses and present a new model of dual role of BCL11B in T-cell malignancies and potential new therapeutic approach, based on recent findings of the function of BCL11B in DNA damage repair. Decreased BCL11B 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 BCL11B 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 BCL11B might be dependent on it. In those cases, targeted inhibition of BCL11B expression may have a therapeutic effect. The antitumor effect of BCL11B suppression might be strengthened by generation of induced T to NK cells (ITNK). Therefore, there is an urgent need to develop a specific BCL11B inhibitor.