Page 278 - Haematologica March 2020

H. de Boussac et al.
MM cells from patients co-cultured with their bone mar- row microenvironment, without detecting significant tox- icity on non-myeloma cells. Our observations greatly implement the previous studies, either on the activity of the molecule alone, in combination with Melphalan and IMiD, or to overcome MM drug resistance.
The maternal embryonic leucine zipper kinase (MELK) inhibitor OTSSP167 also demonstrated therapeutic inter- est. MELK is linked to multiple solid cancer types,37 and recently two groups showed the potential of this inhibitor in MM.33,38 In addition to their work, we demonstrated the synergy between OTSSP167 with Melphalan and
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Figure 7. Kinase inhibitors overcome resistance of Melphalan resistant multiple myeloma cells. (A) Dose response curves of XG7 WT and XG7 MRes cell lines. (B) XG7 WT and XG7 MRes HMCL were cultured for 4 days in 96-well flat-bottom microtiter plates in RPMI 1640 medium, 10% fetal calf serum, 2 ng/mL IL-6 culture medium (control) and graded Melphalan concentrations and selected kinase inhibitors at IC20. At day 4 of culture, the viability was assessed by CellTiter-Glo® Luminescent Cell Viability Assay. Data are mean values ±SD of three independent experiments. P-value: *<0.05; **<0.01; ***<0.001 using a student T-Test for pairs. Mres: Melphalan resistant; SD: standard deviation. WT: wild-type.
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haematologica | 2020; 105(3)