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. 2017 Jan 6;12(1):e0169128. doi: 10.1371/journal.pone.0169128

Fig 4. ACY-957 enhances the anti-leukemic activity of azacitidine in primary AML blasts ex vivo.

Fig 4

(A) Fresh bone marrow samples from AML patients (n = 30) were treated with 3 doses of ACY-957 plus 3 doses of azacitidine. Single agent treatment at 8 doses per drug was performed as well. CI values for 8 combinations were calculated and shown in the squares. The matrix shows one representative bone marrow sample. (B) The median of the 8 CI values was calculated for each sample and plotted. Twenty-two out of 30 samples had a CI value below 1, indicating synergism in majority of the samples tested. (C) Frozen bone marrow samples from AML patients (n = 5) were treated with the indicated doses of ACY-957, azacitidine, ACY-957 plus azacitidine or DMSO and cultured in methylcellulose-based medium for 14 days as in Fig 2G. Colony numbers were quantified and percentage of colonies in DMSO control was plotted. Combination treatment with ACY-957 plus azacitidine significantly reduced colony growth compared to each single agent in 4 out of 5 samples tested. Mean ± SD, n = 3. For all panels, statistical analysis was performed by two-tailed Student’s t-test. * indicates P < 0.05 for all 3 comparisons: combination treatment versus DMSO; combination treatment versus azacitidine alone; combination treatment versus ACY-957 alone.