Figure 2
AML-derived exosomes are elevated and associated with reduced OCN levels in AML patients, are internalized by BM cells, induce splenomegaly, increase LT-HSC population and alter stromal compartment in the BM microenvironment. (a) Plasma exosome numbers measured by NanoSight (left) and plasma OCN levels were determined by ELISA (right) in healthy control (n=12) and AML patients (n=43). (b) Plasma exosome count in AML patients with low (<10 ng/ml, n=29) or high (>10ng/ml, n=14) plasma OCN levels. (c) Overall, 100 μg CFSE-labeled exosomes were co-cultured with BM cells for 4 h. Uptake of CFSE-labeled exosomes by marrow cells was analyzed by fluorescence microscopy. (d) Uptake of CFSE-labeled exosomes by marrow cells was analyzed by FACS analysis for internalization of CFSE-labeled exosomes in indicated BM subpopulations (left). Percent CSFE+ cells within indicated BM subpopulations were summarized (right, n=3 mice in three independent experiments). (e) Six- to eight-week-old B6 mice were injected with either normal human PBMC-derived or AML-derived exosomes. Mice were euthanized 30 days after initial injection. (f) Mouse spleen is weight is summarized (n=5–6 mice per group in at least two independent experiments). (g) Frequency of LT-HSC in BM (n=6–8 mice per group in at least three independent experiments). (h) Frequency of Sca1+, CD146+ and CD166+ cells in the stromal compartment (n=6–8 mice per group in at least three independent experiments). ns, not significant, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
