ArticleThe Journal of clinical investigation2016
LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Interferon signaling gene expression, and DNA methylation interactions in Sjögren's disease via mendelian randomization.iScience · 2026Article
- Shared Genetic Susceptibility Between Asthma and Immune-Mediated Inflammatory Diseases.Canadian respiratory journal · 2026Article
- Reduced Function of the Adaptor SH2B3 Promotes T1D via Altered Cytokine-Regulated, T-Cell-Intrinsic Immune Tolerance.Diabetes · 2025Article
- LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice.Stem cell reviews and reports · 2025Article
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.The Journal of experimental medicine · 2024Article
- Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants.Human genomics · 2022Article
- LNK (SH2B3) inhibition expands healthy and Fanconi anemia human hematopoietic stem and progenitor cells.Blood advances · 2022Article
- Activated interleukin-7 receptor signaling drives B-cell acute lymphoblastic leukemia in mice.Leukemia · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Interleukin-7 receptor α mutational activation can initiate precursor B-cell acute lymphoblastic leukemia.Nature communications · 2021Article
- Structural and functional analysis of target recognition by the lymphocyte adaptor protein LNK.Nature communications · 2021Article
- Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia.Blood advances · 2021Article
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- Leukemia WithFrontiers in oncology · 2021Article
- A New Treatment Strategy for Early T-Cell Precursor Acute Lymphoblastic Leukemia: A Case Report and Literature Review.OncoTargets and therapy · 2021Article
- When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies.Reviews of physiology, biochemistry and pharmacology · 2021Review
- SH2B3, Transcribed by STAT1, Promotes Glioblastoma Progression Through Transducing IL-6/gp130 Signaling to Activate STAT3 Signaling.Frontiers in cell and developmental biology · 2021Article
- Early induction and increased risk of precursor B-cell neoplasms after exposure of infant or young-adult mice to ionizing radiation.Journal of radiation research · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk ALL commonly associated with alterations that affect the tyrosine kinase pathway, tumor suppressors, and lymphoid transcription factors. Loss-of-function mutations in the gene-encoding adaptor protein LNK (also known as SH2B3) are found in Ph-like ALLs; however, it is not clear how LNK regulates normal B cell development or promotes leukemogenesis. Here, we have shown that combined loss of Lnk and tumor suppressors Tp53 or Ink4a/Arf in mice triggers a highly aggressive and transplantable precursor B-ALL. Tp53-/-Lnk-/- B-ALLs displayed similar gene expression profiles to human Ph-like B-ALLs, supporting use of this model for preclinical and molecular studies. Preleukemic Tp53-/-Lnk-/- pro-B progenitors were hypersensitive to IL-7, exhibited marked self-renewal in vitro and in vivo, and were able to initiate B-ALL in transplant recipients. Mechanistically, we demonstrated that LNK regulates pro-B progenitor homeostasis by attenuating IL-7-stimuated JAK/STAT5 signaling via a direct interaction with phosphorylated JAK3. Moreover, JAK inhibitors were effective in prolonging survival of mice transplanted with Lnk-/-Tp53-/- leukemia. Additionally, synergistic administration of PI3K/mTOR and JAK inhibitors further abrogated leukemia development. Hence, our results suggest that LNK suppresses IL-7R/JAK/STAT signaling to restrict pro-/pre-B progenitor expansion and leukemia development, providing a pathogenic mechanism and a potential therapeutic approach for B-ALLs with LNK mutations.
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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.