UGCG inhibition sensitizes CLL cells to ABT-737–induced apoptosis. (A) Annexin V/7-amino-actinomycin D staining with subsequent flow cytometry (n = 9). ABT-737 significantly induced apoptosis in CLL cells (P < .0001). Whereas IgM stimulation protected CLL cells partly from ABT-737-induced apoptosis (P = .0072), UGCG inhibition reverted this effect with a significantly higher amount of apoptotic cells (P = .0021). Data are mean ± SEM of 9 independent experiments. Statistics are calculated by paired t test. (B) Ceramide/glucosylceramide ratio based on mass spectrometric data exemplarily for fatty acyl chain C16:0 (n = 4). Whereas IgM stimulation led to a lower and thereby glucosylceramide-dominated ratio, inhibition of UGCG reverted the ratio toward ceramide with a concomitant higher quotient after BCR engagement. Protection from ABT-737-induced apoptosis by IgM stimulation was measurable by a glucosylceramide-dominated ratio. UGCG inhibition during ABT-737 treatment and BCR cross-linking resulted in a higher apoptosis rate accompanied by a ceramide-influenced ratio.