Fig. 3: Functional BCL-2 dependence indicates preclinical antileukemia activity in vivo.
From: Prediction of venetoclax activity in precursor B-ALL by functional assessment of apoptosis signaling
Individual patient-derived BCP-ALL xenograft samples (N = 12) were transplanted onto pairs of recipient mice and treated with either VEN or vehicle for 10 days. After treatment, mice were tightly monitored for onset of leukemia-related morbidity. a Survival times of leukemia bearing mice treated with VEN (gray bars) or vehicle (black bars) (left diagram) and corresponding VEN-induced survival differences (‘delta survival’, right diagram). b Association of direct VEN priming with preclinical VEN sensitivities of BCP-ALL in vivo (linear regression; R2, correlation coefficient; p, significance) and c predictive value of direct VEN priming for post-VEN survival of treated mice (ROC/receiver operating characteristic curve; AUC, area under the curve; p, significance). d Strong association of functional BCL-2 dependence (mitochondrial BAD-HRK priming) with in vivo VEN responses, and e high predictive value of BAD-HRK priming for survival of VEN treated mice. Preclinical in vivo VEN responses analyzed in larger treatment groups confirming f low (PDX13; N = 8 mice per group), g intermediate (PDX10; N = 10 mice per group), and h strong (PDX2, five mice per group) VEN sensitivity of the respective patient-derived xenograft leukemia observed in the preclinical trial (Kaplan–Meier analysis; p, significance by log-rank test; VEN, venetoclax; CTRL control)
