Page 58 - Haematologica August 2018

R. Mani et al.
mice revealed reduced leukemic burden compared to vehi- cle treated control mice (Figure 5B). The presence of AML in the animals was confirmed in spleen, bone marrow and blood using a multi-color flow cytometric panel (CD45 /CD33/CD34/CD123/CD19/CD3/HLA-DR/murineCD45 /viability stain) and CD123 expression was found to be maintained in vivo in engrafted mice (Figure 5C and Online Supplementary Figure S8-S9).
Discussion
Relapse-free survival is low in AML and MDS in the absence of allogeneic hematopoietic stem cell transplanta- tion. Current therapies, even if targeted for specific sub- types and mutational groups, provide only transient remissions, likely due in part to persistent stem cells.3 The expression of CD123, the alpha chain of IL-3 receptor, is
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Figure 4. Blasts from high-risk MDS express CD123 and are sensitive to SL401. (A-B) SL-401 depletes CD123+ MDS blasts. MDS samples cultured with vehicle or SL-401 (1 μg/ml, 2 μg/ml) for 120 hours were stained for various myeloid markers (CD45, CD33, CD34, CD123, and viability stain) and live cells were counted. (A) Representative MDS-RAEB cells cultured with varying doses of SL-401 for 120 hours. Density plots gated on live CD45+ population are shown. (B) Live CD34+ blast concentration (bars), live CD34+ blast % (red lines) and live lymphoid % (green lines) are shown for each sample (N=6 CD123+ MDS) P=0.0183 for live CD34+ blast concentration between SL401 1 μg/ml vs. vehicle, and P=0.0063 for live CD34+ blast concentration between SL401 2 μg/ml vs. vehicle. CD123– MDS sample (MDS 1) was included as a control.
haematologica | 2018; 103(8)