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. 2015 Jan;56(1):226-9.
doi: 10.3109/10428194.2014.910657. Epub 2014 Jun 17.

Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies (V体育官网)

James M Bogenberger  1 , Devora Delman, Nanna Hansen, Riccardo Valdez, Veena Fauble, Ruben A Mesa, Raoul Tibes
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"V体育2025版" Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies

James M Bogenberger et al. Leuk Lymphoma. 2015 Jan.
No abstract available

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Conflict of interest statement

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www. informahealthcare VSports手机版. com/lal.

Figures

Figure 1
Figure 1
5-Azacytidine synergy in combination with ABT-199 or ABT-737. 5-Azacytidine was applied to ex vivo cultures as a single dose upon experiment initiation and the readout for synergy analyses with CalcuSyn was relative cell number as measured with Cell Titer-Glo (Promega) at 96 h. (A) Combination index (CI) values for 2.5 µM 5-azacytidine combined with the indicated dose range of ABT-199 or ABT-737. Row headings in (A) correspond to the 4–6 dose labels for ABT-199 or ABT-737 plotted in CI versus fractional effect plots shown in (C), and as listed in brackets under each CI value in (A). Label “1” corresponds to the highest dose of ABT compound, while labels “4” to “6” correspond to the lowest dose. Nine doses of 5-azacytidine and six doses of each ABT compound were tested in all experiments; however, higher ABT compound doses were necessarily dropped for CalcuSyn analysis if they did not fit into the linear range of response. (B) Single-agent activity of ABT-199 and ABT-737. Nanomolar ABT concentrations are plotted on the x-axis, while relative cell number expressed as a fraction of the buffer treated control cells is plotted on the y-axis. For AML_2, MDS_1 and CMML_1 equipotent doses of each ABT compound were used, whereas AML_1 and AML_3 received different dose ranges for each ABT compound. (C) CI versus fractional effect plots for ABT-199 and ABT-737. CI values < 0.9 are synergistic, 0.9–1.1 are nearly additive and > 1.1 are antagonistic. A fractional effect of 0 is the minimal effect, while 1 is the maximal effect. (D) Median-effect plots for 5-azacytidine, ABT-199 and ABT-737 treatments. r-Values for each drug dose–response fit are listed in the lower right corner of each plot.
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References

    1. Bogenberger JM, Kornblau SM, Pierceall WE, et al. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies. Leukemia. 2014 Jan 23; [Epub ahead of print] - PMC - PubMed
    1. Tsao T, Shi Y, Kornblau S, et al. Concomitant inhibition of DNA methyltransferase and BCL-2 protein function synergistically induce mitochondrial apoptosis in acute myelogenous leukemia cells. Ann Hematol. 2012;91:1861–1870. - PMC (V体育安卓版) - PubMed
    1. Pan R, Hogdal LJ, Benito JM, et al. Selective BCL-2 inhibition by ABT-199 causes on target cell death in acute myeloid leukemia. Cancer Discov. 2014;4:362–375. - PMC - PubMed
    1. Bogenberger JM, Pierceall WE, Lena R, et al. BH3 profiling predicts 5-azacytidine response in malignant myeloid cells. Blood. 2012;120(Suppl. 1) Abstract 1432.
    1. Tibes R, Kornblau SM, Pierceall WE, et al. BH3 profiling as predictor of 5-azacytidine and decitabine clinical responses. Blood. 2013;122:603.

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