Fig. 8: EMDR contributes to tumor heterogeneity upon relapse.
a Muller plots of sensitive and individual BTZ resistant (Res) sub-clones from simulations described in a-c. Colors denote different subclones. Red arrow indicates start of BTZ treatment. b Images of GFP + U266 (green) and RFP + PSR (red) MM cells and cell nuclei (DAPI; blue) in tibial sections of mice from in vivo study described in Fig. 7. Magnification 20X. Scale bar 50 microns. c Relative quantification of GFP + U266 and PSR MM in tibial sections described in Fig. 8b. Vehicle = 5 tibia, Zol = 5 tibia, Zol+BTZ = 7 tibia, BTZ = 4 tibia. Values are mean ± SD. d Mean number of resistant sub-clones arising following BTZ treatment tumors that reached 20% with resistant subclones and the locations within the bone marrow microenvironment where each subclone originated, with/without EMDR from simulations described in a. The n number represents the number of simulations that developed resistance out of the 25 independent simulations. n = 13/25 (No Treatment), n = 10/25 (No EMDR + BTZ), n = 24/25 (EMDR + BTZ). Values are mean ± SD. Statistical significance was determined by two-way ANOVA with a Å Ãdák’s multiple comparison (c) or Tukey’s test (d). Source data are provided as a Source Data file for c and d. Source data for a can be accessed at DOI 10.17605/OSF.IO/TNAX9.
