Glucocorticoids (GCs) are fundamental components of most chemotherapies employed against lymphoid malignancies because they cause apoptosis and cell cycle arrest. In this study we investigate the possible role of a novel splice variant of human BCL2L11/Bim, termed BB, for GC-induced apoptosis. First evidence for BB was obtained by Affymetrix-based whole genome comparative expression profiling, where a corresponding probe set was found to be induced in 8 of the 13 ALL children and 1 adult during systemic GC monotherapy (Schmidt et al., 2006). The postulated BB mRNA consists of the 5’ portion of Bim (up to and including the BH3-containing exon 8) and the 3’ portion of Bam, a cDNA originally discovered in a multiple myeloma cDNA library (Claudio et al., 2002). Thus, it encodes a putative protein consisting of the N-terminal region of Bim (including its BH3 domain) and 40 C-terminal amino acids derived from Bam and not present in any known Bim transcript. BB and Bim proteins have similar molecular masses and could not be distinguished by conventional Western technology when probed by α-Bim antibody as most α-Bim antibodies recognize the N-terminal region which is common to both isoforms. RT-PCR data and protein analyses carried out by using α-Bam antibody (that recognizes the Bam specific C-terminal region) on GC-treated CEM-C7H2 cells supported the existence of the postulated BB mRNA and protein. Subcellular localization analysis of BB suggested that BB may be directed to mitochondria, ascribed probably to its BH3-domain interaction with other BCL2 proteins and not by its unique C-terminus which in contrast to the Bim C-terminus doesn't localize to mitochondria. The functional analyses with conditional overexpression in ALL in vitro model revealed that overexpressed BB is a killer protein with potency similar to that of Bim and thus may contribute to the anti-leukemic effects of GCs and perhaps other apoptotic responses.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1029.