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High-throughput approaches to uncover synergistic drug combinations in leukemia.

Publication ,  Journal Article
Chory, EJ; Wang, M; Ceribelli, M; Michalowska, AM; Golas, S; Beck, E; Klumpp-Thomas, C; Chen, L; McKnight, C; Itkin, Z; Wilson, KM; Holland, D ...
Published in: SLAS discovery : advancing life sciences R & D
June 2023

We report a comprehensive drug synergy study in acute myeloid leukemia (AML). In this work, we investigate a panel of cell lines spanning both MLL-rearranged and non-rearranged subtypes. The work comprises a resource for the community, with many synergistic drug combinations that could not have been predicted a priori, and open source code for automation and analyses. We base our definitions of drug synergy on the Chou-Talalay method, which is useful for visualizations of synergy experiments in isobolograms, and median-effects plots, among other representations. Our key findings include drug synergies affecting the chromatin state, specifically in the context of regulation of the modification state of histone H3 lysine-27. We report open source high throughput methodology such that multidimensional drug screening can be accomplished with equipment that is accessible to most laboratories. This study will enable preclinical investigation of new drug combinations in a lethal blood cancer, with data analysis and automation workflows freely available to the community.

Duke Scholars

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Published In

SLAS discovery : advancing life sciences R & D

DOI

EISSN

2472-5560

ISSN

2472-5552

Publication Date

June 2023

Volume

28

Issue

4

Start / End Page

193 / 201

Related Subject Headings

  • Myeloid-Lymphoid Leukemia Protein
  • Leukemia, Myeloid, Acute
  • Humans
  • Histone-Lysine N-Methyltransferase
  • Drug Evaluation, Preclinical
  • Drug Combinations
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chory, E. J., Wang, M., Ceribelli, M., Michalowska, A. M., Golas, S., Beck, E., … Stanton, B. Z. (2023). High-throughput approaches to uncover synergistic drug combinations in leukemia. SLAS Discovery : Advancing Life Sciences R & D, 28(4), 193–201. https://doi.org/10.1016/j.slasd.2023.04.004
Chory, Emma J., Meng Wang, Michele Ceribelli, Aleksandra M. Michalowska, Stefan Golas, Erin Beck, Carleen Klumpp-Thomas, et al. “High-throughput approaches to uncover synergistic drug combinations in leukemia.SLAS Discovery : Advancing Life Sciences R & D 28, no. 4 (June 2023): 193–201. https://doi.org/10.1016/j.slasd.2023.04.004.
Chory EJ, Wang M, Ceribelli M, Michalowska AM, Golas S, Beck E, et al. High-throughput approaches to uncover synergistic drug combinations in leukemia. SLAS discovery : advancing life sciences R & D. 2023 Jun;28(4):193–201.
Chory, Emma J., et al. “High-throughput approaches to uncover synergistic drug combinations in leukemia.SLAS Discovery : Advancing Life Sciences R & D, vol. 28, no. 4, June 2023, pp. 193–201. Epmc, doi:10.1016/j.slasd.2023.04.004.
Chory EJ, Wang M, Ceribelli M, Michalowska AM, Golas S, Beck E, Klumpp-Thomas C, Chen L, McKnight C, Itkin Z, Wilson KM, Holland D, Divakaran S, Bradner J, Khan J, Gryder BE, Thomas CJ, Stanton BZ. High-throughput approaches to uncover synergistic drug combinations in leukemia. SLAS discovery : advancing life sciences R & D. 2023 Jun;28(4):193–201.

Published In

SLAS discovery : advancing life sciences R & D

DOI

EISSN

2472-5560

ISSN

2472-5552

Publication Date

June 2023

Volume

28

Issue

4

Start / End Page

193 / 201

Related Subject Headings

  • Myeloid-Lymphoid Leukemia Protein
  • Leukemia, Myeloid, Acute
  • Humans
  • Histone-Lysine N-Methyltransferase
  • Drug Evaluation, Preclinical
  • Drug Combinations