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M. Schneeweiss et al.
and Figure 5C). Together, these data suggest that DCC- 2618 counteracts growth of AHN cells, including CMML monocytes and AML blasts.
DCC-2618 inhibits the proliferation of neoplastic eosinophils
Advanced SM is often accompanied by eosinophilia. In addition PDGFRA is a known target of DCC-2618. We analyzed the effects of DCC-2618 on proliferation and
A
survival of the FIP1L1-PDGFRA (F/P) positive EOL-1 cell line. DCC-2618 was found to inhibit proliferation in EOL-1 cells at low nanomolar range of concentrations (IC50: 1.8±1.3 nM) (Online Supplementary Figure S6A). Similar effects were seen with DP-5439 (Online Supplementary Figure S6A). DCC-2618 also induced apop- tosis in EOL-1 cells (Online Supplementary Figure S6C). Next, we examined the effects of DCC-2618 on growth of primary eosinophils. In these experiments, DCC-2618
B
Figures 3. DCC-2618 and DP-5439 induce apoptosis in neoplastic mast cells. HMC-1, ROSA (A) and MCPV-1 (B) were incubated in control medium (0 μM) or medium containing various concentrations of DCC-2618 and DP-5439, as indicated, at 37°C for 48 h. Cells were then harvested and the percentage of apoptotic cells was quantified morphologically on Wright-Giemsa-stained cytospin preparations (left panels) or by flow cytometry (determination of annexinV/PI-positive cells, right pan- els). Results represent the mean±S.D. of three independent experiments. Asterisk (*): P<0.05 compared to control medium.
haematologica | 2018; 103(5)