5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax . . . - PubMed Results: In this study, we demonstrate that venetoclax and 5-Aza act synergistically to kill AML cells in vitro and display combinatorial antitumor activity in vivo We uncover a novel nonepigenetic mechanism for 5-Aza-induced apoptosis in AML cells through transcriptional induction of the proapoptotic BH3-only protein NOXA
5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-Mediated . . . Note that 1 0 × 10 7 cells, for AML cell lines, and 2 5 × 10 5 cells per well, for primary AML cells, were treated with DMSO or 0 3, 1, or 3 μmol L of 5-Aza, for 6 and 24 hours, at which point the cells were washed with 10 mL of cold DPBS and spun down at 4°C, 300 rcf for 5 minutes The supernatant was removed, and the cells were lysed with
Acquired resistance to venetoclax plus azacitidine in acute myeloid . . . In comparison, THP-1 and OCI-AML3 cell lines showed IC 50 of 358 0 nM and 430 6 nM, respectively (Fig 1 A) These results demonstrate that MV4-11 and ML-2 cell lines are sensitive to VEN + AZA, while THP-1 and OCI-AML3 cell lines are inherently much less sensitive to the combination therapy (Fig 1 A)
Venetoclax and azacitidine compared with induction chemotherapy for . . . Venetoclax (ven) plus azacitidine (aza) is superior to aza alone for patients with newly diagnosed acute myeloid leukemia (AML) who are unsuitable candidates for intensive chemotherapy (IC) 1 Ven aza is a well-tolerated regimen with high response rates and the potential for deep and durable remissions, 2-5 prompting questions related to
Mechanisms of Azacitidine Chemotherapy Resistance in AML and MDS and . . . AZA-R subclones together with parental AZA-sensitive cells were profiled using cytogenetics and NGS (TruSight Myeloid Sequencing, Illumina) Some of these drugs were shown to effectively substitute AZA on the parental cell lines (Venetoclax IC=0 9µM, Ruxolitinib IC50=1 7µM, Sorafenib IC50=5 3µM) Whether AZA enhanced sensitivity to these
Investigating resistance to 5-Azacytidine and Venetoclax in PDX models . . . (A) Comparison of the effect of 5-Azacytidine (AZA), Venetoclax (VEN), Panobinostat (PAN), Dinaciclib (DIN) and Sorafenib (SOR) in primary MDS AML cells and the AZA-resistant OCI-M2 cell line (B) Comparison of IC50 values of following inhibitors: 5-Azacytidine (AZA), hypomethylating agent; Venetoclax (VEN), BCL2 inhibitor; Dinaciclib (DIN
Panobinostat sensitizes AraC-resistant AML cells to the combination of . . . MTT assay results show IC 50 s (VEN + AZA, 1:3) of below 500 nM (presented as VEN concentration) for the three lines with acquired AraC resistance (MOLM-13 AraC-R, MV4-11 AraC-R, and U937 AraC-R IC 50 s were 426 8 nM, 124 9 nM, and 351 6 nM, respectively) and 1171 nM for THP-1 cells (Fig 1 A) The cells were then treated with VEN + AZA for 24