Page 55 - Haematologica August 2018

Activity of SL-401 in AML and MDS
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Figure 1. AML cells express CD123 and can be targeted with SL-401. (A) SL-401 induces cytotoxicity in patient-derived AML blasts. AML blasts were cultured with varying doses of SL-401 and viability was measured at 24 and 48 hr (N=16; Trend: 24hr difference = -42.13, P<0.0001 and 48hr difference =-91.59, P<0.0001). Only AML samples >50% viable by PI staining were used for the analysis. (B) SL-401 inhibits clonogenicity of AML cells. Representative images of AML colony from vehicle treated plates are shown (PH 4X EVOS® XL Core imaging system). Leukemic colonies were counted 10-14 days after plating AML cells with continuous pres- ence of vehicle or SL-401(1 μg/ml) in duplicates. Only AML samples that formed at least 15 colonies (more than 20 cells per colony) or clusters (5-20 cells per clus- ter) in vehicle treated plates were used for the analysis. Each dot represents average of duplicate plates for an AML sample (N=5 AML). (C) FLT3-ITD+ AML are sen- sitive to SL-401(same samples in Figure 1A). (D) Expression of CD123 in AML cell lines MV4-11 and MOLM-13 as determined by flow cytometry. (E) Growth inhibition by SL-401 in MV4-11 and MOLM-13 cells. Cells (0.5x106/ml) were treated with vehicle or SL-401 (100ng/ml and 1 μg/ml) and cell viability was measured after 72 hrs.
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