Fig. 4: Treatment with HHT depletes the HSC population in BM-derived primary FPD-MM cells and exerts in vitro synergistic anti-leukemia activity. | Blood Cancer Journal

Fig. 4: Treatment with HHT depletes the HSC population in BM-derived primary FPD-MM cells and exerts in vitro synergistic anti-leukemia activity.

From: Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM)

Fig. 4

A Primary FPD-MM18 cells were treated with 100 nM of HHT for 16 h and single cell RNA-Seq (scRNA-Seq) analysis was performed. SingleR analysis was utilized to define cell clusters. The UMAP plot shows defined cell populations. B Log2 fold-change in mRNA expressions due to HHT treatment in the HSC population. C GMR-AML1 cells were treated with the indicated concentrations of HHT for 18 h. Following this, immunoblot analyses were conducted on total cell lysates. The expression of β-actin in the lysates served as the loading control. D Patient-derived FPD-MM18 cells were treated with 100 nM of HHT for 18 h. Cells were harvested and analyzed by CyTOF analysis utilized a cocktail of rare metal element-tagged antibodies. Leukemia stem cells were defined by high expression of CLEC12A(CLL-1), CD117, and CD123 and low expression of CD244, CD86, and CD11b. Heat map shows the absolute fold-change of significantly altered protein expressions in the treated over control cells. E GMR-AML1 cells were treated with the indicated concentrations of HHT and/or venetoclax for 48 h. Then the percentage annexin V-positive apoptotic cells was determined by flow cytometry. Delta synergy scores (ZIP) were determined using SynergyFinder v3.0 web application.

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