Figure 2. Axl expression and sensitivity to TP-0903 (tartrate salt) in CLL B-cells from patients on ibrutinib treatment.
(A) Surface Axl expression. This was determined on purified leukemic B-cells obtained from CLL patients currently on ibrutinib therapy (n=22) or who progressed while on ibrutinib (n=2; P6, P7) or who were scheduled for ibrutinib treatment (n=2; P25, P26) by flow cytometry using a specific antibody to Axl. The “0” indicates time point before ibrutinib treatment started. (B) Sensitivity to TP-0903. Purified CLL B-cells from blood samples of patients currently on ibrutinib therapy (n=22) or who progressed while on ibrutinib (n=2; P6, P7) or who were scheduled for ibrutinib treatment (n=2; P25, P26) were treated with increasing doses of TP-0903 (0.01–0.50μM) for 24 hours. Apoptosis induction was determined by flow cytometry after staining with Annexin/PI. Numbers depicted on horizontal axis are time points (months) when patient samples were collected from ibrutinib initiation. LD50 dose depicted on the vertical axis is calculated from the apoptosis measurement under the different TP-0903 concentrations. CLL patients (P1–P26) are indicated by arbitrary numbers.