Fig. 2

Combination of 5-AZA and venetoclax is highly effective after HMA failure despite dose adjustment. a CD34⁺ BMMNCs from patients with Myelodysplastic Syndromes (MDS) or secondary acute myeloid leukemia (sAML) were treated for 72 h with venetoclax (VEN), 5-azacitidine (5-AZA), alone or in combination. Cell viability was measured by flow cytometry using Annexin V and 7AAD staining. Data are presented as mean ± standard deviation (SD) of the ratio between viable cells after a 72 h treatment with drug or vehicle (DMSO). One-way ANOVA resulted in p < 0.0001. The results from post hoc pairwise comparison are reported in figure. b CD34⁺ BMMNCs from patients with MDS intermediate risk (INT) (according to IPSS) or sAML and failure of hypomethylating agent (HMA) were treated for 72 h with venetoclax (VEN), 5-AZA or the combination of both at the indicated concentrations. Cell viability was measured by flow cytometry using Annexin V and 7AAD staining. Data points representing the same patient are depicted in the same colour. Shown is the ratio between viable cells after a 72 h inhibitor or vehicle treatment (DMSO) with the mean and standard deviation (SD). One-way ANOVA resulted in p = 0.0025. The results from post hoc pairwise comparison are reported in figure. c BMMNCs (1 × 10⁴) from patient #12, #13 and #14 as described in b with sAML or high-risk MDS (according to IPSS) after HMA failure were plated in methylcellulose after 72 h of treatment with Venetoclax (VEN), 5-AZA or the combination of both at the indicated concentrations. The total number of colonies was determined at day 10 to 14. Experiments were performed in duplicates. One-way ANOVA resulted in p = 0.0005 for patient #12, p = 0.015 for patient #13, and p = 0.0068 for patient #14. The results from post hoc pairwise comparison are reported in figure