GATA-1: one TEF customer.

lenalidomide. The results of this trial indicate that CLL patients who have initially received lenalidomide can have enhanced clinical responses with the addition of rituximab (Chanan-Khan, verbal communication, July 2008). Until there is a clear dissection of the exact mechanisms of rituximab-mediated clearances of CLL B cells, it would seem premature to alter current strategies. However, this work does make a very strong case for further studies of monoclonal antibodies in xenograft mouse models where the timing of lenalidomide and other monoclonal antibodies targeted to CLL B cells is tested. This study also found that lenalidomidemediated internalization of CD20 can be used to enhance the ability to deliver oligonucleotidebased therapy by using CD20 immune liposomes. The investigators are to be congratulated for recognizing that the internalization of CD20 could be a novel approach for delivery of treatment vectors, such as microRNA or siRNA, that can target critical molecules in CLL B cells. This latter finding underscores the fact that the investigation of drugs such as lenalidomide must be continued not only to determine the exact nature of the mechanism of action in the presence or absence of other drugs/monoclonal antibodies but also in the context of specific diseases. In total, this work has shown the “yin and yang” of lenalidomide: decreases in rituximab-mediated ADCC of CLL B cells by NK cells when CLL B cells are preincubated with the drug, increases in ADCC if NK cells are first exposed to lenalidomide, and increases in CD23 and CD38 but reduced membrane levels of CD20 via internalization. Further work in CLL and other B-cell malignancies that evaluate the key mechanisms of action for lenalidomide toward leukemic/ lymphoma cells are surely going to uncover critical information for the clinical trialist. Conflict-of-interest disclosure: The author declares no competing financial interests. ■