ArticleMolecular systems biology2022
Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL.
Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Interpretable multi-omics integration across mixed-order tensors with MANTRA.Molecular systems biology · 2026Article
- Resistance pathways and next-generation treatments in chronic lymphocytic leukemia.Discover oncology · 2026Review
- High-content imaging of primary chronic lymphocytic leukemia cells predicts patient cohorts with distinct cellular drug responses.iScience · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs).Cell death discovery · 2024Article
- Disrupting pro-survival and inflammatory pathways with dimethyl fumarate sensitizes chronic lymphocytic leukemia to cell death.Cell death & disease · 2024Article
- Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial.Nature cancer · 2023Article
- Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies.Blood advances · 2023Article
- The Immunology of DLBCL.Cancers · 2023Review
- Recent revelations and future directions using single-cell technologies in chronic lymphocytic leukemia.Frontiers in oncology · 2023Review
- Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL.Molecular systems biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumour microenvironment and genetic alterations collectively influence drug efficacy in cancer, but current evidence is limited and systematic analyses are lacking. Using chronic lymphocytic leukaemia (CLL) as a model disease, we investigated the influence of 17 microenvironmental stimuli on 12 drugs in 192 genetically characterised patient samples. Based on microenvironmental response, we identified four subgroups with distinct clinical outcomes beyond known prognostic markers. Response to multiple microenvironmental stimuli was amplified in trisomy 12 samples. Trisomy 12 was associated with a distinct epigenetic signature. Bromodomain inhibition reversed this epigenetic profile and could be used to target microenvironmental signalling in trisomy 12 CLL. We quantified the impact of microenvironmental stimuli on drug response and their dependence on genetic alterations, identifying interleukin 4 (IL4) and Toll-like receptor (TLR) stimulation as the strongest actuators of drug resistance. IL4 and TLR signalling activity was increased in CLL-infiltrated lymph nodes compared with healthy samples. High IL4 activity correlated with faster disease progression. The publicly available dataset can facilitate the investigation of cell-extrinsic mechanisms of drug resistance and disease progression.
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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.