ArticleThe Journal of biological chemistry2015
Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor Specificities.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Tofacitinib as a Successful Treatment for Hyper-IgE Syndrome and Autoimmunity Associated with Constitutive Activation of JAK3.Journal of clinical immunology · 2026Article
- The Mechanisms of Resistance to JAK Inhibitors in Lymphoid Leukemias: A Scoping Review of Evidence from Preclinical Models and Case Reports.International journal of molecular sciences · 2025Article
- Interleukin-7 enhances recruitment of MDSCs by regulating MCP-1 via JAK1/STAT3 signaling pathway in non-small cell lung cancer.Scientific reports · 2025Article
- Drug Repositioning via Graph Neural Networks: Identifying Novel JAK2 Inhibitors from FDA-Approved Drugs through Molecular Docking and Biological Validation.Molecules (Basel, Switzerland) · 2024Article
- Janus Kinase 3 (JAK3): A Critical Conserved Node in Immunity Disrupted in Immune Cell Cancer and Immunodeficiency.International journal of molecular sciences · 2024Review
- Pharmacophore-Based Virtual Screening and Experimental Validation of Pyrazolone-Derived Inhibitors toward Janus Kinases.ACS omega · 2022Article
- JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2022Article
- In vivo impact of JAK3 A573V mutation revealed using zebrafish.Cellular and molecular life sciences : CMLS · 2022Article
- Deregulation of the Interleukin-7 Signaling Pathway in Lymphoid Malignancies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Identification of U937Frontiers in oncology · 2021Article
- Janus Kinase Mutations in Mice Lacking PU.1 and Spi-B Drive B Cell Leukemia through Reactive Oxygen Species-Induced DNA Damage.Molecular and cellular biology · 2020Article
- Failure of tofacitinib to achieve an objective response in aCold Spring Harbor molecular case studies · 2020Article
- Article
- JAK/STAT Pathway Mutations in T-ALL, Including the STAT5B N642H Mutation, are Sensitive to JAK1/JAK3 Inhibitors.HemaSphere · 2019Article
- Article
- Are peptides a solution for the treatment of hyperactivated JAK3 pathways?Inflammopharmacology · 2019Review
- Janus kinase 2 activation mechanisms revealed by analysis of suppressing mutations.The Journal of allergy and clinical immunology · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
JAK1 and JAK3 are recurrently mutated in acute lymphoblastic leukemia. These tyrosine kinases associate with heterodimeric cytokine receptors such as IL-7 receptor or IL-9 receptor, in which JAK1 is appended to the specific chain, and JAK3 is appended to the common gamma chain. Here, we studied the role of these receptor complexes in mediating the oncogenic activity of JAK3 mutants. Although JAK3(V674A) and the majority of other JAK3 mutants needed to bind to a functional cytokine receptor complex to constitutively activate STAT5, JAK3(L857P) was unexpectedly found to not depend on such receptor complexes for its activity, which was induced without receptor or JAK1 co-expression. Introducing a mutation in the FERM domain that abolished JAK-receptor interaction did not affect JAK3(L857P) activity, whereas it inhibited the other receptor-dependent mutants. The same cytokine receptor independence as for JAK3(L857P) was observed for homologous Leu(857) mutations of JAK1 and JAK2 and for JAK3(L875H). This different cytokine receptor requirement correlated with different functional properties in vivo and with distinct sensitivity to JAK inhibitors. Transduction of murine hematopoietic cells with JAK3(V674A) led homogenously to lymphoblastic leukemias in BALB/c mice. In contrast, transduction with JAK3(L857P) induced various types of lymphoid and myeloid leukemias. Moreover, ruxolitinib, which preferentially blocks JAK1 and JAK2, abolished the proliferation of cells transformed by the receptor-dependent JAK3(V674A), yet proved much less potent on cells expressing JAK3(L857P). These particular cells were, in contrast, more sensitive to JAK3-specific inhibitors. Altogether, our results showed that different JAK3 mutations induce constitutive activation through distinct mechanisms, pointing to specific therapeutic perspectives.
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