Since anergy is a hallmark of CLL (9, 21), we established a gene signature contributing to the anergic state of CLL cells, which includes Cbl-b, Grail, Egr2 and the tyrosine kinase Lck. Chromatin-immunoprecipitation studies in primary human CLL cells further resulted in the first report of Lck as a NFAT2 target gene in CLL (16, 22). Here, CBLB is linked to B-cell chronic lymphocytic leukemia.