Joos S, Otano-Joos MI, Ziegler S, Brüderlein S, du Manoir S, Bentz M, Möller P, and Lichter P. Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 87: 1571-1578

Deutsches Krebsforschungszentrum, Abt. Organisation komplexer Genome, Heidelberg, Germany.
Blood (Impact Factor: 10.45). 03/1996; 87(4):1571-8.
Source: PubMed


Primary mediastinal (thymic) B-cell lymphoma is a high-grade non-Hodgkin's lymphoma with unique features. By using comparative genomic hybridization and interphase cytogenetics, 26 tumors were analyzed to identify genomic imbalances. Gains of chromosomal material were much more frequent than losses (110 v 10) and involved chromosomes 9p, 12q, and Xq (31% to 50%). Interestingly, gain of Xq coincided with gain of 9p. Distinct high-level amplifications were found in four subregions. In 2 cases, amplifications of proto-oncogene REL were shown by filter hybridization, indicating a possible pathogenic role of this gene. The characteristic pattern of chromosomal imbalances distinct from other B-cell lymphomas suggests a specific pathway of genetic changes associated with this lymphoma.

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    • "Nuclear localisation of REL, one of the NFκB complex proteins, is related to the activation of the NFκB pathway. Genomic gains and amplifications of the REL protooncogene locus on the short arm of chromosome 2p are present in over half of the PMBCL cases and associated with the nuclear position of REL [25, 26]. JAK-STAT is another major pathway responsible for the regulation of cell proliferation. "
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    ABSTRACT: Primary mediastinal B-cell lymphoma (PMBCL) is a relatively rare lymphoma subtype affecting mainly young adults. Its molecular signature and clinical features resemble classical Hodgkin lymphoma. The optimal chemotherapy for this lymphoma subtype has not been established. The addition of rituximab to anthracycline based chemotherapy improved response rates and survival. Many centers use R-CHOP as standard treatment, but the role of the intensified regimens and consolidation radiotherapy has to be clarified. Recent data coming from retrospective analyses and an ongoing prospective study addressing the problem of consolidation radiotherapy will help to better identify risk groups and apply risk-adapted and effective treatment strategies. The latest research has helped to understand molecular mechanisms of PMBCL pathogenesis and indicated targets of directed therapy for the future.
    Current Hematologic Malignancy Reports 06/2014; 9(3). DOI:10.1007/s11899-014-0219-0 · 2.20 Impact Factor
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    • "Recent studies have highlighted many genetic similarities as well. Both entities show gains at 2p15 (REL locus) and 9p24 (JAK2 locus) and breaks at CIITA (38% of PMBCL and 15% of cHL) [18–20]. The presence of CIITA rearrangement significantly correlates with shorter disease-specific survival for patients with PMBCL [20]. "
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    ABSTRACT: The current classification of lymphoid neoplasms is based on clinical information, morphology, immunophenotype, and molecular genetic characteristics. Despite technical and scientific progress, some aggressive B-cell lymphomas with features overlapping between two different types of lymphomas remain difficult to classify. The updated 2008 World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues has addressed this problem by creation of two new provisional categories of B-cell lymphomas, unclassifiable; one with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and the second with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. We review here the diagnostic criteria of these two provisional entities and discuss new scientific findings in light of the 2008 WHO classification.
    Advances in Hematology 04/2012; 2012(5, supplement):460801. DOI:10.1155/2012/460801
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    • "In addition, PMBL and HL share oncogenic mechanisms, including activation of the NF-kB pathway (Lam et al., 2005; Rosenwald et al., 2003; Savage et al., 2003). A recurrent genomic copy number gain in these lymphomas involves a region on chromosome band 9p24, which occurs in 35%–45% of PMBL cases (Joos et al., 1996; Lenz et al., 2008; Meier et al., 2009; Rosenwald et al., 2003) and 33% of HL cases (Joos et al., 2000, 2003). One gene in this interval is JAK2, which encodes a tyrosine kinase that mediates signaling downstream of several cytokine receptors (Bentz et al., 2001; Joos et al., 2003, 2000; Meier et al., 2009; Rosenwald et al., 2003). "
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    ABSTRACT: Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases.
    Cancer cell 12/2010; 18(6):590-605. DOI:10.1016/j.ccr.2010.11.013 · 23.52 Impact Factor
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