ArticleThe Journal of clinical investigation2018
Drug-perturbation-based stratification of blood cancer.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Advances and Perspectives in the Treatment of T-PLL.Current hematologic malignancy reports · 2020Pooled it
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- Identification of two epitypes of IGHV unmutated chronic lymphocytic leukemia with distinct B-cell-related epigenetic imprinting and genetic alterations.HemaSphere · 2026Article
- From 2D cultures to 3D systems: evolving cancer models at the interface of functional precision medicine and theranostics.Theranostics · 2026Review
- The Chronic Lymphocytic Leukemia Epigenome: A Powerful and Stable Framework for Understanding Biological and Clinical Heterogeneity.Hematology/oncology clinics of North America · 2025Review
- Image-based drug screening combined with molecular profiling identifies signatures and drivers of therapy resistance in pediatric AML.Cell reports. Medicine · 2025Article
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- Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target.Nature communications · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- Clinical Utility of Patient-Derived Cell-Based In Vitro Drug Sensitivity Testing for Optimizing Adjuvant Therapy in Dogs with Solid Tumors: A Retrospective Study (2019-2023).Animals : an open access journal from MDPI · 2025Article
- BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia.Molecular cancer · 2025Article
- Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.Nature communications · 2025Article
- BiomiX, a user-friendly bioinformatic tool for democratized analysis and integration of multiomics data.BMC bioinformatics · 2025Article
- Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Drug-Induced Differential Gene Expression Analysis on Nanoliter Droplet Microarrays: Enabling Tool for Functional Precision Oncology.Advanced healthcare materials · 2025Article
- SUMO: an R package for simulating multi-omics data for methods development and testing.Bioinformatics advances · 2025Article
- Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify 2 clinicobiological subtypes.Blood advances · 2024Article
- Article
- Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.Biomedicines · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
51 authors at 15 institutions in 8 countries.
Funding
Abstract
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non-BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
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Registered trials
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.