ArticleBlood2010
Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.
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162 citing papers in PubMed, 1 synthesis or guideline pooled it, 322 citations in OpenAlex.
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- A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers.International journal of hematology · 2013Trial
- Trial
- Genetic Variants Associated with Life Expectancy in Patients with Chagas Disease.Medical sciences (Basel, Switzerland) · 2026Article
- The LNK adaptor protein: a dual regulator of proliferation and migration in solid tumors.Molecular & cellular oncology · 2026Review
- Molecular characterization of pediatric mastocytosis revealed different somatic mutations with uncertain prognostic value.Frontiers in cell and developmental biology · 2026Article
- Diagnostic relevance of SH2B3 mutations in suspected myeloid malignancies and acute leukemia: insights from a large-scale NGS-based screening study.Blood cancer journal · 2025Article
- Donor selection for allogeneic hematopoietic cell transplant in a patient with JAK2 V617F primary myelofibrosis and SH2B3/LNK germline variant.Annals of hematology · 2024Article
- Myeloproliferative Neoplasms: Challenging Dogma.Journal of clinical medicine · 2024Review
- Real-World Impact of Deep Targeted Sequencing on Erythrocytosis and Thrombocytosis Diagnosis: A Reference Centre Experience.Cancers · 2024Article
- Germline bi-allelicHaematologica · 2024Article
- Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience.Molecular diagnosis & therapy · 2024Article
- Review
- Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci.The Journal of clinical endocrinology and metabolism · 2024Article
- The Missing LNK: Evolution from Cytosis to Chronic Myelomonocytic Leukemia in a Patient with Multiple Sclerosis and Germline SH2B3 Mutation.Case reports in genetics · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.Circulation · 2021Article
- The JAK/STAT signaling pathway: from bench to clinic.Signal transduction and targeted therapy · 2021Review
- Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing.Life (Basel, Switzerland) · 2021Review
- New Markers of Disease Progression in Myelofibrosis.Cancers · 2021Review
102 more citing papers are in PubMed but not listed here.
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10 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling due to activation of tyrosine kinases is a common feature of myeloid malignancies. Here we report the first human disease-related mutations in the adaptor protein LNK, a negative regulator of JAK-STAT signaling, in 2 patients with JAK2 V617F-negative myeloproliferative neoplasms (MPNs). One patient exhibited a 5 base-pair deletion and missense mutation leading to a premature stop codon and loss of the pleckstrin homology (PH) and Src homology 2 (SH2) domains. A second patient had a missense mutation (E208Q) in the PH domain. BaF3-MPL cells transduced with these LNK mutants displayed augmented and sustained thrombopoietin-dependent growth and signaling. Primary samples from MPN patients bearing LNK mutations exhibited aberrant JAK-STAT activation, and cytokine-responsive CD34(+) early progenitors were abnormally abundant in both patients. These findings indicate that JAK-STAT activation due to loss of LNK negative feedback regulation is a novel mechanism of MPN pathogenesis.
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