{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:20:56Z","timestamp":1783488056174,"version":"3.55.0"},"reference-count":78,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype\u2013phenotype correlation in Epstein-Barr virus\u2013positive (EBV+) and EBV\u2013 PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-\u03baB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6\/JAK\/STAT signaling, NF-\u03baB activity, and MYC signaling. Moreover, class I major histocompatibility complex\u2013mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase\/AKT\/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV\u2013 PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas.<\/jats:p>","DOI":"10.1182\/bloodadvances.2021005486","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T20:54:16Z","timestamp":1635540856000},"page":"637-651","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways"],"prefix":"10.1182","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-7125","authenticated-orcid":false,"given":"Hanno M.","family":"Witte","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany;"},{"name":"Department of Hematology and Oncology, Federal Armed Forces Hospital Ulm, Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-2105","authenticated-orcid":false,"given":"Axel","family":"K\u00fcnstner","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Group, and"},{"name":"Institute for Cardiogenetics, University of L\u00fcbeck, L\u00fcbeck, Germany;"},{"name":"University Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Hertel","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany;"},{"name":"H\u00e4matopathologie L\u00fcbeck, Reference Centre for Lymph Node Pathology and Hematopathology, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Wolfram","family":"Bernd","sequence":"additional","affiliation":[{"name":"H\u00e4matopathologie L\u00fcbeck, Reference Centre for Lymph Node Pathology and Hematopathology, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Bernard","sequence":"additional","affiliation":[{"name":"H\u00e4matopathologie L\u00fcbeck, Reference Centre for Lymph Node Pathology and Hematopathology, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"St\u00f6lting","sequence":"additional","affiliation":[{"name":"H\u00e4matopathologie L\u00fcbeck, Reference Centre for Lymph Node Pathology and Hematopathology, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Merz","sequence":"additional","affiliation":[{"name":"H\u00e4matopathologie L\u00fcbeck, Reference Centre for Lymph Node Pathology and Hematopathology, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-8947","authenticated-orcid":false,"given":"Nikolas","family":"von Bubnoff","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany;"},{"name":"University Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-4521","authenticated-orcid":false,"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[{"name":"Medical Systems Biology 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