Figure 2

CD38 expression of AML cells is regulated by microenvironmental cues and induced upon ATRA treatment. (A) Mean fluorescence intensity (MFI) of CD38 on primary AML cells (n = 10) and healthy peripheral blood mononuclear cells (n = 6) measured by flow cytometry, mono-, co- or triple-cultured with HUVEC and/or mesenspheres before and after treatment with 0.1 µM all-trans-retinoic acid (ATRA), data normalized to mono-cultured control. (B) primary AML cells (n = 10) were mono-, co- or triple-cultured with HUVEC and/or mesenspheres. ATRA or vehicle was added at 0.1 µM for 2 days followed by daratumumab treatment at 0.1 µg/ml or vehicle for another 3 days. Absolute numbers of CD45⁺ cells were normalized to mono-cultured control. Each dot represents the mean of triplicates, for each pair the mean change in cell count is given in percentage. (C) Correlation of anti-leukemic activity of daratumumab given as mean cell-count reduction with CD38 expression given as MFI measured by flow cytometry for each primary AML sample, mono-, co- or triple-cultured with HUVEC and/or mesenspheres (n = 10 different AML donors, each primary sample was tested in triplicate). Data are shown as mean ± SEM. n.s., not significant, *p < 0.05 **p < 0.01 ***p < 0.001 as determined by paired one-way ANOVA (A), Wilcoxon signed-rank test (B) and linear regression (C). See also Supplementary Fig. S2.