ArticleBlood2020
IL10RA modulates crizotinib sensitivity in NPM1-ALK+ anaplastic large cell lymphoma.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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.
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Who cites it
29 citing papers in PubMed, 29 citations in OpenAlex.
- Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study.Journal of translational medicine · 2025Trial
- Integrative Drug-Target Causal Analysis, Single-Cell Sequencing and In-Vivo Validation for Dissecting Molecular Mechanisms Underlying Focal Epilepsy.CNS neuroscience & therapeutics · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.Blood advances · 2025Article
- HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy.Leukemia · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Advances in peripheral T cell lymphomas: pathogenesis, genetic landscapes and emerging therapeutic targets.Histopathology · 2025Review
- Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.Nature communications · 2024Article
- STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.Cell reports. Medicine · 2024Article
- ALK fusions in the pan-cancer setting: another tumor-agnostic target?NPJ precision oncology · 2023Review
- A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors.Communications biology · 2023Article
- Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib.British journal of haematology · 2023Article
- Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.Science translational medicine · 2023Article
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- Article
- PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.Molecular cancer · 2022Article
- Review
- Review
- Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma.Blood · 2022Article
- Regulation of CD45 phosphatase by oncogenic ALK in anaplastic large cell lymphoma.Frontiers in oncology · 2022Article
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Authors and funding
39 authors at 20 institutions in 9 countries.
Funding
Abstract
Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1 (NPM1)-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54% to 90% in clinical trials; however, a subset of patients progressed within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation and knockout screens in ALCL cell lines, combined with RNA sequencing data derived from ALK inhibitor-relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of interleukin 10 receptor subunit alpha (IL10RA). Elevated IL10RA expression rewires the STAT3 signaling pathway, bypassing otherwise critical phosphorylation by NPM1-ALK. IL-10RA expression does not correlate with response to standard chemotherapy in pediatric patients, suggesting that a combination of crizotinib and chemotherapy could prevent ALK inhibitor resistance-specific relapse.
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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.