ArticleOncogene2016
Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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
31 citing papers in PubMed, 44 citations in OpenAlex.
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- Nucleophosmin 1 proteins as potential therapeutic targets in non-communicable chronic inflammatory diseases: a review of pathophysiological mechanisms.Frontiers in cell and developmental biology · 2026Review
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway.Cancers · 2023Article
- Exploiting signaling rewiring in cancer cells with co-existing oncogenic drivers.Molecular oncology · 2023Article
- Nuclear NPM-ALK Protects Myc from Proteasomal Degradation and Contributes to Its High Expression in Cancer Stem-Like Cells in ALK-Positive Anaplastic Large Cell Lymphoma.International journal of molecular sciences · 2023Article
- Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.Science translational medicine · 2023Article
- Novel TENM3-ALK fusion is an alternate mechanism for ALK activation in neuroblastoma.Oncogene · 2022Article
- De novo generation of the NPM-ALK fusion recapitulates the pleiotropic phenotypes of ALK+ ALCL pathogenesis and reveals the ROR2 receptor as target for tumor cells.Molecular cancer · 2022Article
- Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.Frontiers in oncology · 2022Review
- Review
- NPM-ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation.Cancer research · 2021Article
- EBP2, a novel NPM-ALK-interacting protein in the nucleolus, contributes to the proliferation of ALCL cells by regulating tumor suppressor p53.Molecular oncology · 2021Article
- Resistance to histone deacetylase inhibitors confers hypersensitivity to oncolytic reovirus therapy.Blood advances · 2020Article
- Article
- Non-translational Connections of eEF1B in the Cytoplasm and Nucleus of Cancer Cells.Frontiers in molecular biosciences · 2020Review
- Proteomic Phosphosite Analysis Identified Crucial NPM-ALK-Mediated NIPA Serine and Threonine Residues.International journal of molecular sciences · 2019Article
- NPM-ALK Is a Key Regulator of the Oncoprotein FOXM1 in ALK-Positive Anaplastic Large Cell Lymphoma.Cancers · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
Abstract
Most of the anaplastic large-cell lymphoma (ALCL) cases carry the t(2;5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase). NPM-ALK-deregulated kinase activity drives several pathways that support malignant transformation of lymphoma cells. We found that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. Only the cytoplasmic portion was catalytically active in both cell lines and primary ALCL, whereas the nuclear portion was inactive because of heterodimerization with NPM1. Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus. Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) increased phosphorylation and cell death through the engagement of an ATM/Chk2- and γH2AX (phosphorylated H2A histone family member X)-mediated DNA-damage response. Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a consequence of ERK1/2 hyperactivation. Altogether, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via oncogenic stress responses. A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic option in cells that become resistant by NPM-ALK amplification.
Indexed as
Identifiers
What OpenQuestion holds
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.