Page 87 - Haematologica - Vol. 105 n. 6 - June 2020

PRIMA-1Met and AZA combination in TP53-mutant MDS/AML
nation, we observed a dose-dependent reversal of the inhibition of cell proliferation (Figure 7C). The relative proliferation of APR + AZA treated cells at day 3 was sig- nificantly higher when FLT3-L was added (P<0.01) (Figure
AB
7D). This reversal of the inhibitory effect on proliferation was associated with a decrease in apoptosis, since 40% of the cells stained positive for Annexin V with the drug combination treatment without FLT3-L compared with
CD
EF
Figure 3. Effects of PRIMA-1Met (APR-246, APR) on primary cells from TP53-mutated myelodysplastic syndromes (MDS) / acute myeloid leukemia (AML) patients and healthy donors. The median numbers of (A) myeloid and (B) erythroid colonies relative to the untreated control for 34 bone marrow samples from MDS/AML patients treated with APR, azacitidine (AZA), or the combination APR + AZA in semi-solid medium (methylcellulose). Relative numbers of (C) myeloid and (D) erythroid colonies according to the TP53 status (WT: wild-type) treated with APR or the combination of APR + AZA. Median numbers of (E) myeloid and (F) erythroid colonies relative to untreated control for 3 CD34+ cells from healthy donors treated with APR, AZA or the combination APR + AZA. *P<0.05, ****P<0.0001.
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