ArticlePloS one2013
t(8;9)(p22;p24)/PCM1-JAK2 activates SOCS2 and SOCS3 via STAT5.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- The IL-1R and NFKBIZ pathway mediates immunoregulatory responses and immunotherapy efficacy in anaplastic large cell lymphoma.Leukemia · 2026Article
- Analysis and therapeutic targeting of the IL-1R pathway in anaplastic large cell lymphoma.Blood · 2023Article
- Primary cutaneous gamma/delta T-cell lymphoma with simultaneous JAK2 and TP63 rearrangements: a new double-hit?Histopathology · 2023Article
- Moving towards biologically informed treatment strategies for T-cell lymphomas.International journal of hematology · 2023Review
- How molecular advances may improve the diagnosis and management of PTCL patients.Frontiers in oncology · 2023Review
- Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.EMBO molecular medicine · 2022Article
- Genomic Aberrations Generate Fusion Gene FOXK2::TP63 and Activate NFKB1 in Cutaneous T-Cell Lymphoma.Biomedicines · 2022Article
- Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas.International journal of molecular sciences · 2021Review
- Article
- SENP1 promotes MCL pathogenesis through regulating JAK-STAT5 pathway and SOCS2 expression.Cell death discovery · 2021Article
- A novel model of alternative NF-κB pathway activation in anaplastic large cell lymphoma.Leukemia · 2021Article
- Next generation sequencing of breast implant-associated anaplastic large cell lymphomas reveals a novel STAT3-JAK2 fusion among other activating genetic alterations within the JAK-STAT pathway.The breast journal · 2021Article
- The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia andCold Spring Harbor molecular case studies · 2020Article
- Deregulated expression of NKL homeobox genes in T-cell lymphomas.Oncotarget · 2019Article
- Genetic alterations of 9p24 in lymphomas and their impact for cancer (immuno-)therapy.Virchows Archiv : an international journal of pathology · 2019Article
- Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.Nature communications · 2018Article
- RecurrentBlood · 2018Article
- Peripheral T-cell lymphoma cell line T8ML-1 highlights conspicuous targeting of PVRL2 by t(14;19)(q11.2;q13.3).Haematologica · 2017Article
- Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1/STAT3 mutations.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- JAK2 V617F Mutation in Adult T Cell Leukemia-Lymphoma.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2016Article
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Fusions of the tyrosine kinase domain of JAK2 with multiple partners occur in leukemia/lymphoma where they reportedly promote JAK2-oligomerization and autonomous signalling, Affected entities are promising candidates for therapy with JAK2 signalling inhibitors. While JAK2-translocations occur in myeloid, B-cell and T-cell lymphoid neoplasms, our findings suggest their incidence among the last group is low. Here we describe the genomic, transcriptional and signalling characteristics of PCM1-JAK2 formed by t(8;9)(p22;p24) in a trio of cell lines established at indolent (MAC-1) and aggressive (MAC-2A/2B) phases of a cutaneous T-cell lymphoma (CTCL). To investigate signalling, PCM1-JAK2 was subjected to lentiviral knockdown which inhibited 7 top upregulated genes in t(8;9) cells, notably SOCS2/3. SOCS3, but not SOCS2, was also upregulated in a chronic eosinophilic leukemia bearing PCM1-JAK2, highlighting its role as a central signalling target of JAK2 translocation neoplasia. Conversely, expression of GATA3, a key T-cell developmental gene silenced in aggressive lymphoma cells, was partially restored by PCM1-JAK2 knockdown. Treatment with a selective JAK2 inhibitor (TG101348) to which MAC-1/2A/2B cells were conspicuously sensitive confirmed knockdown results and highlighted JAK2 as the active moiety. PCM1-JAK2 signalling required pSTAT5, supporting a general paradigm of STAT5 activation by JAK2 alterations in lymphoid malignancies. MAC-1/2A/2B--the first JAK2-translocation leukemia/lymphoma cell lines described--display conspicuous JAK/STAT signalling accompanied by T-cell developmental and autoimmune disease gene expression signatures, confirming their fitness as CTCL disease models. Our data support further investigation of SOCS2/3 as signalling effectors, prognostic indicators and potential therapeutic targets in cancers with JAK2 rearrangements.
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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.