Figure 6.

Relapsed myelomas are more sensitive to MTI-101. Specimens were separated into two groups depending on clinical diagnosis; either newly diagnosed or relapsed patients. (A) CD138+ cells were treated with 10 µM of MTI-101 for 24 hr. After 24 hr cell death was measured by Annexin V staining and FACS analysis. CD138 cells derived from patients which have relapsed on therapy were significantly more sensitive to MTI-101 induced cell death compared to CD138 cells obtained from newly diagnosed patients (p < 0.05, Student’s t-test) (B) CD138+ cells were pretreated with 50 µM 2APB or VC (vehicle control) for 30 min and then were treated with 10 µM MTI-101 for 24 hrs followed by FACS analysis. (C) Dose response surfaces for primary MM cells from patients treated ex vivo with bortezomib (50–0.6 nM, 3 fold serial dilution), MTI-101 (20–0.25 uM, 3 fold serial dilultions)) and combination. Exposure time was 96 hrs except for patient pt129 (60 hrs). The actual combination of MTI-101 and bortezomib (MTI-101 + BTZ) is more effective (higher kill) than theoretical additive effect (ADDITIVE) indicating synergy between two drugs. Combination indexes (CI) were calculated using CalcuSyn software at 30 and 60 hrs. Samples were performed in duplicate and independent combination indexes were calculated for each patient specimen.