Evidence map›Paper›PMID 37121274›Full record

ArticleSLAS discovery : advancing life sciences R & D2023

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

Emma J Chory, Meng Wang, Michele Ceribelli, Aleksandra M Michalowska, Stefan Golas, Erin Beck, Carleen Klumpp-Thomas, Lu Chen, Crystal McKnight, Zina Itkin and 8 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in SLAS discovery : advancing life sciences R & D, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 1 country.

Emma J ChoryMedia Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.. Electronic address: emma.chory@duke.edu.
Meng WangNationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, OH, USA.
Michele CeribelliDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Aleksandra M MichalowskaDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Stefan GolasMedia Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Erin BeckDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Carleen Klumpp-ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Lu ChenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Crystal McKnightDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Zina ItkinDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Kelli M WilsonDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
David HollandDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.
Sanjay DivakaranCardio-Oncology Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
James BradnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Javed KhanGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Berkley E GryderGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, United States.
Craig J ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville MD 20850, USA.; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Benjamin Z StantonNationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Biological Chemistry & Pharmacology, The Ohio State University College of Medicine, Columbus, OH, USA.. Electronic address: Benjamin.Stanton@nationwidechildrens.org.
National Center for Advancing Translational Sciences · USNational Institutes of Health · USNationwide Children's Hospital · USBrigham and Women's Hospital · USBroad Institute · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · US

Funding

Research Services Section (RSS)ZICTR000242 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WILSON, KELLI · 2015 to 2025
$64.9M
BIOINFORMATICS: SYSTEMS BIOLOGY OF PEDIATRIC CANCERSZIABC011002 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KHAN, JAVED · 2009 to 2025
$9.3M
Targeting High-risk Neuroblastoma using high through put siRNA screeningZIABC010806 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KHAN, JAVED · 2009 to 2025
$7.8M
HTS enabled examination of drug combinationsZIATR000047 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2025
$7.1M
Histone Acetylation Dynamics and Epigenome DuplicationR01GM144601 · NIGMS · OHIO STATE UNIVERSITY · PI PARTHUN, MARK R · 2022 to 2025
$1.6M
Genomic incorporation of stapled peptides for cost effective discovery and synthesis of novel therapeuticsF32CA247274 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHORY, EMMA J · 2020 to 2022
$201k
NCI NIH HHS F32 CA247274NIGMS NIH HHS R01 GM144601
6 · The paper itself

Abstract

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.

Indexed as

Leukemia, Myeloid, AcuteMyeloid-Lymphoid Leukemia ProteinDrug CombinationsDrug Evaluation, PreclinicalHistone-Lysine N-MethyltransferaseHumansDrug CombinationsHistone-Lysine N-MethyltransferaseMyeloid-Lymphoid Leukemia ProteinAcute myeloid leukemiaCombination indexCombination therapyEpigeneticsOpen-source automationPrecision medicineSynergy

Identifiers

PMID37121274
PMCPMC10449086
OpenAlexW4367396241

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.