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. Author manuscript; available in PMC: 2019 Apr 5.
Published in final edited form as: Leukemia. 2018 Sep 11;33(4):918–930. doi: 10.1038/s41375-018-0254-2

Figure 6: AML cells alter their EV cargo upon UPR induction.

Figure 6:

(a) Expression analysis of BMP genes in Molm-14-mGFP cells cultured in thapsigargin. Fold change determined by 2-ΔΔCt against vehicle-treated cells. Error bars are standard error of the mean from (n=4, two separate experiments). Significance was determined using ANOVA and Bonferroni correction. *P<0.05, **P<0.01. (b) Timecourse of BMP gene expression in explanted Molm-14-mGFP. Molm-14-mGFP cells were sorted out of xenograft bone marrow based on human CD45 expression and cultured ex vivo. RNA was extracted from cells directly from the sort (0hr) or 48 and 72hrs in normal culture media in vitro. Fold change determined by 2-ΔΔCt against in vitro cultured Molm-14-mGFP cells. Error bars are standard error of the mean from (n=7, two separate experiments). (c) Expression analysis of BMP genes from AML patient samples. Fold change determined by 2-ΔΔCt in pairwise analysis against control samples. Error bars are standard error of the mean. (d) Concentration of BMP2 protein in the supernatant (SN) and pellet (EV) from EV harvest of Molm-14-mGFP cells cultured in thapsigargin. ELISA was used to determine protein concentration. Error bars are standard error of the mean from three separate experiments. Significance was determined by ANOVA and Student’s t-test. *P<0.05, **P<0.01. (e) Model for AML-mediated remodeling of the endosteal niche. Niche homeostasis is maintained by reciprocal crosstalk between stromal and hematopoietic components (left). AML proliferation results in an intrinsic UPR that is transferred to stromal cells in part by increased EV output and BMP2 incorporation into EVs. This signaling axis promotes ER stress in recipient stroma and contribute to the differential fates of MSCs and OPCs (right).