Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells

Interleukin-7 (IL-7) and IL-15 have been recently identified as growth fact ors for cutaneous T-cell lymphoma (CTCL) cells, and they protect these cell s from cell death. Using the CTCL cell line SeAx as a test system now shows that IL-7 and IL-15 are indeed necessary to maintain high levels of bcl-2. The up-regulation of bcl-2 was paralleled by increased DNA-binding activit ies of the transcription factors STAT2, STAT5, STAT6, and c-Myb to bcl-2 ge ne promoter-enhancer elements. Because STAT5 and c-Myb positively regulate bcl-2, IL-7 and IL-15 may mediate some of their effects on cell death survi val gene expression through these 2 factors. Constitutive activities of the 3 STAT factors and C-Myb were found in the IL-7- and IL-15-Independent CTC L cell lines HUT78 and MyLa 2059. The c-Myb protein was also present in CTC L cells of the skin lesions of all investigated patients. These results ind icate that IL-7 and IL-15 may Increase bcl-2 expression In CTCL cells by th e activation of c-myb and STAT factors. (C) 2001 by The American Society of Hematology.