Open AccessJournal Article
JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma
Katrien Van Roosbroeck,Luk Cox,Thomas Tousseyn,Idoya Lahortiga,Olga Gielen,Barbara Cauwelier,P De Paepe,Gregor Verhoef,Peter Marynen,Peter Vandenberghe,Chris Peeters,Jan Cools,Iwona Wlodarska +12 more
TLDR
In this paper, the authors showed that the t(4,9,q21,p24)-involving translocation of JAK2 leads to a novel SEC31A-JAK2 fusion, which is oncogenic in vitro and acts as a constitutively activated tyrosine kinase.Abstract:
The genetics of classical Hodgkin lymphoma (cHL) is poorly understood. The finding of a JAK2-involving t(4;9)(q21;p24) in 1 case of cHL prompted us to characterize this translocation on a molecular level and to determine the prevalence of JAK2 rearrangements in cHL. We showed that the t(4;9)(q21;p24) leads to a novel SEC31A-JAK2 fusion. Screening of 131 cHL cases identified 1 additional case with SEC31A-JAK2 and 2 additional cases with rearrangements involving JAK2. We demonstrated that SEC31A-JAK2 is oncogenic in vitro and acts as a constitutively activated tyrosine kinase that is sensitive to JAK inhibitors. In vivo, SEC31A-JAK2 was found to induce a T-lymphoblastic lymphoma or myeloid phenotype in a murine bone marrow transplantation model. Altogether, we identified SEC31A-JAK2 as a chromosomal aberration characteristic for cHL and provide evidence that JAK2 rearrangements occur in a minority of cHL cases. Given the proven oncogenic potential of this novel fusion, our studies provide new insights into the pathogenesis of cHL and indicate that in at least some cases, constitutive activation of the JAK/STAT pathway is caused by JAK2 rearrangements. The finding that SEC31A-JAK2 responds to JAK inhibitors indicates that patients with cHL and JAK2 rearrangements may benefit from targeted therapies.read more
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Hodgkin disease: Hodgkin andReed-Sternberg cells picked from histological sections showclonal immunoglobulin gene rearrangements andappear tobederived fromB cells atvarious stages ofdevelopment
TL;DR: In this article, the authors isolated HRScells by micromanipulation fromhistologicalsections of three cases ofHodgkinlymphoma and analyzed individual cells for immunoglobulin variable (V) gene rear-rangements by PCR.
Journal ArticleDOI
Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy
Michael R. Green,Scott J. Rodig,Przemyslaw Juszczynski,Jing Ouyang,Papiya Sinha,Evan O'Donnell,Donna Neuberg,Margaret A. Shipp +7 more
TL;DR: AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade.
Journal ArticleDOI
STAT3: a multifaceted oncoprotein.
Aleks C. Guanizo,Chamira Dilanka Fernando,Chamira Dilanka Fernando,Daniel J. Garama,Daniel J. Garama,Daniel J. Gough,Daniel J. Gough +6 more
TL;DR: A review of recent studies reveal that STAT3 is either oncogenic or a tumour suppressor, with emerging complexities in the biochemical regulation of STAT3 activity.
Journal ArticleDOI
The arrival of JAK inhibitors: advancing the treatment of immune and hematologic disorders.
Yasuko Furumoto,Massimo Gadina +1 more
TL;DR: The principles of cytokines signaling are reviewed, the current knowledge of the approved inhibitors is summarized, and some of the inhibitors that are currently under development are introduced.
Journal ArticleDOI
The role of the Janus-faced transcription factor PAX5-JAK2 in acute lymphoblastic leukemia
Dagmar Schinnerl,Klaus Fortschegger,Maximilian Kauer,João R. M. Marchante,Reinhard Kofler,Monique L. den Boer,Sabine Strehl +6 more
TL;DR: Together, the data show that PAX5-JAK2 simultaneously deregulates the PAX5 downstream transcriptional program and activates the Janus kinase-STAT signaling cascade and thus, by interfering with these two important pathways, may promote leukemogenesis.
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