Figure 1.
Cell line and patient samples demonstrate variable sensitivity to venetoclax. Isolated malignant cells from patient samples and 4 human-derived CTCL cell lines were incubated with a range of concentrations of venetoclax for 72 hours from which IC50s and Hill slopes were calculated. The median and mean IC50 for patient samples were 102 nM and 833 nM, respectively. (A) Patient samples in order of IC50. Patients were grouped into high responders and low responders using hierarchical cluster analysis. (B) Representative dose-response curves for patient samples (i) and CTCL cell lines (ii). (C) Comparison of Hill slopes between patient samples and cell lines. The difference between them would suggest distinct methods of actions. (D) Patient samples are most likely to be sensitive to venetoclax in more advanced disease. Stage based on ISCL classification.43 (E) Patient samples classified as Sézary syndrome (SS) are more likely than mycosis fungoides (MF) patients to be sensitive to venetoclax.