ArticleOncogene2015
Juvenile myelomonocytic leukaemia-associated mutation in Cbl promotes resistance to apoptosis via the Lyn-PI3K/AKT pathway.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 20 citations in OpenAlex.
- Genomic Characterization of RTK-RAS Pathway Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Medical sciences (Basel, Switzerland) · 2026Article
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Long non-coding RNA small nucleolar RNA host gene 29 drives chronic myeloid leukemia progression via microRNA-483-3p/Casitas B-lineage Lymphoma axis-mediated activation of the phosphoinositide 3-kinase/Akt pathway.Medical oncology (Northwood, London, England) · 2024Article
- Review
- Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Haematologica · 2022Article
- Article
- Green barley mitigates cytotoxicity in human lymphocytes undergoing aggressive oxidative stress, via activation of both the Lyn/PI3K/Akt and MAPK/ERK pathways.Scientific reports · 2019Article
- Article
- Article
- Cbl-mediated K63-linked ubiquitination of JAK2 enhances JAK2 phosphorylation and signal transduction.Scientific reports · 2017Article
- Structural Determinants of the Gain-of-Function Phenotype of Human Leukemia-associated Mutant CBL Oncogene.The Journal of biological chemistry · 2017Article
- The anti-apoptotic form of tyrosine kinase Lyn that is generated by proteolysis is degraded by the N-end rule pathway.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Juvenile myelomonocytic leukaemia (JMML) is an aggressive myeloproliferative neoplasm in children characterized by granulocyte macrophage colony-stimulating factor (GM-CSF) hypersensitivity and resistance to chemotherapy. We recently identified c-Cbl (henceforth referred to as Cbl) as a GM-CSF receptor (GMR) responsive protein that targets Src for ubiquitin-mediated destruction upon GM-CSF stimulation and showed that a loss of negative regulation of Src is pivotal in the hyperactivation of GMR signalling in JMML cells. However, the mechanism regulating the chemoresistant nature of JMML has remained largely unknown. Here, we show that the JMML-associated Cbl mutant in complex with the Src family kinase Lyn promotes Cbl's adapter function, leading to increased association to PI3K regulatory subunit p85 and Lyn-dependent AKT pro-survival signalling. Notably, molecular or pharmacologic inhibition of the Lyn-PI3K/AKT pathway, but not the Ras/mitogen-activated protein kinase signalling axis, markedly increased the sensitivity of the otherwise chemoresistant Cbl mutant-JMML cells to chemotherapeutic agents currently used in the treatment of JMML patients. These results support the potential translational benefit of combining modalities that inhibit Lyn-PI3K/AKT signalling with traditional antileukaemia agents in the management of JMML.
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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.