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K.N. Smitheman et al.
GSK2879552, ATRA, or the combination of GSK2879552 plus ATRA at two different time points. For most cell lines and time points, a smaller number of gene expression changes are found in the single treatments compared to the combination (Figure 3A and B and Online Supplementary Figure S3A and B). In addition, a large set of genes is found exclusively differentially expressed in com- bination versus DMSO, indicating that there is an effect
from the combination of treatments not present in the sin- gle agent treatments (Figure 3A and B and Online Supplementary Figure S3A and B). The overlap of signifi- cantly differentially expressed genes under combination treatment for each time point in four cell lines (OCI- AML3, MOLM-13, MV4-11, and THP-1) is shown in Figure 3C (top). This indicates that a portion of genes are found in all four cell lines at each time point (intersect).
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Figure 6. Acute myeloid leukemia (AML) blast colony forming ability is impaired in AML patient-derived samples treated with a combination of LSD1 inhibitor plus all-trans retinoic acid (ATRA). (A) Dose response of AML blast colony formation of patient sample AML0007 treated with a titration of GSK2879552 ± 100 nM ATRA or a titration of ATRA. Three replicate wells per concentration were tested. (B) Maximum percent of inhibition achieved for patient sample AML0007 treated with 100 nM ATRA or calculated from the GSK2879552 dose response curves + 100 nM ATRA. (C) IC50 values of the GSK2879552 dose response curves ± 100 nM ATRA for patient sample AML0007. (D-F) Same as (A-C) for patient-derived sample 4031113SH.
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haematologica | 2019; 104(6)