Fig. 9: JUN/AP-1 activity is required for chemotherapy resistance.
From: Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance
a Experimental design to investigate whether enforced JUN expression confers chemotherapy resistance on patient leukemia cells. mCherry-expressing, doxycycline-inducible JUN or TagBFP-transduced MSK011 patient leukemia cells are labeled with CFSE and transplanted into NSG mice under doxycycline diet in vivo, followed by combined AraC and DXR chemotherapy in vivo. Free illustration materials from Kenq Net (https://www.wdb.com/kenq/illust/mouse) and SciDraw (https://doi.org/10.5281/zenodo.4152947 and https://doi.org/10.5281/zenodo.5204473) are used. b Representative flow cytometry plots (for 5 biological replicates) to analyze bone marrow human leukemia cells isolated from mice transplanted with MSK011 patient leukemia cells containing mCherry-expressing, JUN or TagBFP-transduced cells, corresponding to Fig. 9c–f. c, d Combined AraC and DXR chemotherapy treatment reduces total human CD45-positive (c) and mCherry expressing (d) human leukemia cell numbers in mouse bone marrow, regardless of JUN or TagBFP transduction (two-tailed Welch’s t test p = 7.9 × 10−4 and 1.3 × 10−2 for CD45-positive cell numbers of TagBFP and JUN; 1.5 × 10−3 and 1.4 × 10−2 for mCherry-positive cell numbers of TagBFP and JUN, respectively). Bars represent mean values of 5 biological replicates. e, f There is no significant difference in fold reduction of total human leukemia cell numbers in AraC/DXR-treated mice relative to vehicle-treated mice between JUN versus TagBFP transduction group (two-tailed Welch’s t test p = 0.074; l), whereas mCherry-positive JUN-expressing cells exhibit increased resistance to AraC/DXR treatment compared to mCherry-positive TagBFP-expressing cells (two-tailed Welch’s t test p = 0.030). Bars represent the mean values of 5 biological replicates. Source data are provided as a Source Data file.
