Expression and glucocorticoid-regulation of “Bam”, a novel BH3-only transcript in acute lymphoblastic leukemia

Abstract

Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by glucocorticoids (GC) is a central component in the therapy of acute lymphoblastic leukemia (ALL), and defining its molecular basis and that of GC resistance is crucial for therapeutic improvements. We recently identified a novel transcript from the BCL2L11/Bim locus, termed "Bam", by affymetrix based whole genome expression profiling performed on 27 children (13 were already published) with ALL and many additional biological systems. Most children that induced Bam also induced Bim as well, in some cases Bam induction was more pronounced than that of Bim and in one patient only the Bam, but not Bim was induced. In C7H2, PreB697, Jurkat-GR(wt) and GC-sensitive (S-lines), this transcript was induced by GC in a translation-independent manner, suggesting that direct transcriptional induction of this BH3-only molecule by GC might cause apoptosis in at least ALL children and other biological systems.