Primary lymphoma of the central nervous system: just DLBCL or not?

Montesinos‐Rongen, Manuel; Siebert, Reiner; Deckert, Martina

doi:10.1182/blood-2008-04-149005

Cited by 72 publications

(63 citation statements)

References 32 publications

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“…Furthermore, PCNSLs show intraclonal diversity resulting from ongoing SHM (5,8). Collectively, there is strong evidence for selection of PCNSL cells by Ag(s) (5,6,8,9), suggesting that Ag recognition plays a role in the pathogenesis of PCNSL. Furthermore, the intriguing question arises as to the existence of extranodal SHM in the CNS, which is of fundamental immunological relevance beyond PCNSL.…”

Section: Discussionmentioning

confidence: 99%

“…PCNSL cells correspond to late germinal center (GC) exit B cells with surface IgM expression (3,4); they are characterized by rearranged and somatically mutated Ig genes with a high Ig genemutation frequency (5)(6)(7)(8). Collectively, these features, which indicate participation of the tumor cells in a prolonged GC reaction, as well as the restricted Ig VH gene repertoire with a biased usage of the IGVH4-34 gene segment and evidence for ongoing somatic hypermutation (SHM), provide strong evidence for Ag selection for expression of a functional BCR (5,8,9). This has raised the intriguing hypothesis that Ags within the CNS may stimulate the tumor cells and may play a role in the pathogenesis of PCNSL similar to follicular lymphoma (FL), MALT lymphoma, and chronic lymphocytic leukemia (CLL), for which several Ags recently were identified (10)(11)(12).…”

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confidence: 99%

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Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins

Montesinos‐Rongen

Purschke

Brunn

et al. 2015

The Journal of Immunology

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Primary lymphoma of the CNS (PCNSL) is a diffuse large B cell lymphoma confined to the CNS. To elucidate its peculiar organ tropism, we generated recombinant Abs (recAbs) identical to the BCR of 23 PCNSLs from immunocompetent patients. Although none of the recAbs showed self-reactivity upon testing with common autoantigens, they recognized 1547 proteins present on a large-scale protein microarray, indicating polyreactivity. Interestingly, proteins (GRINL1A, centaurin-α, BAIAP2) recognized by the recAbs are physiologically expressed by CNS neurons. Furthermore, 87% (20/23) of the recAbs, including all Abs derived from IGHV4-34 using PCNSL, recognized galectin-3, which was upregulated on microglia/macrophages, astrocytes, and cerebral endothelial cells upon CNS invasion by PCNSL. Thus, PCNSL Ig may recognize CNS proteins as self-Ags. Their interaction may contribute to BCR signaling with sustained NF-κB activation and, ultimately, may foster tumor cell proliferation and survival. These data may also explain, at least in part, the affinity of PCNSL cells for the CNS.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins

Montesinos‐Rongen

Purschke

Brunn

et al. 2015

The Journal of Immunology

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“…51 In PCNSL, recurrent gains in 18q have been described by various groups. 1,[5][6][7]10 18q21 harbors the BCL2 and MALT1 genes. MALT1 complexes with BCL10 and a CARD protein to activate the nuclear factor-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 They are classified as diffuse large B-cell lymphoma (DLBCL). 3,4 However, it is still a matter of debate whether they differ from systemic DLBCL with respect to their molecular features and pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma

et al. 2009

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To determine the pattern of genetic alterations in primary central nervous system lymphomas (PCNSL), 19 PCNSL were studied by high-density single-nucleotide polymorphism arrays. Recurrent losses involved 6p21.32, 6q21, 8q12-12.2, 9p21.3, 3p14.2, 4q35.2, 10q23.21 and 12p13.2, whereas gains involved 18q21-23, 19q13.31, 19q13.43 and the entire chromosomes X and 12. Partial uniparental disomies (pUPDs) were identified in 6p and 9p21.3. These genomic alterations affected the HLA locus, the CDKN2A/p16, CDKN2B/p15 and MTAP, as well as the PRDM1, FAS, MALT1, and BCL2 genes. Increased methylation values of the CDKN2A/p16 promoter region were detected in 75% (6/8) PCNSL. Gene expression profiling showed 4/21 (20%) minimal common regions of imbalances to be associated with a differential mRNA expression affecting the FAS, STAT6, CD27, ARHGEF6 and SEPT6 genes. Collectively, this study unraveled novel genomic imbalances and pUPD with a high resolution in PCNSL and identified target genes of potential relevance in the pathogenesis of this lymphoma entity.

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“…If there are indeed differing molecular genetic subtypes of VRL, this may explain the variable clinical courses of VRL patients. However, GEP data from primary CNS lymphoma suggest that the centrally-located DLBCL may not be so easily classified into the molecular subgroups described for the peripheral DLBCL: 70 considering the similarities between VRL and primary CNS lymphoma, this may also apply to VRL. The GEP classification of DLBCL according to other genes, for example, those involved in host inflammatory response, 48 may also be relevant for VRL when taking into account the immune privileged status of the eye.…”

Section: Vitreoretinal Lymphomamentioning

confidence: 99%

Molecular pathology of lymphoma

Coupland

2012

Eye

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Ocular lymphomas can be divided into intraocular lymphomas and ocular adnexal lymphomas. The vitreoretinal lymphomausually a diffuse large B-cell lymphoma (DLBCL) of high-grade malignancy-is the most common lymphoid malignancy arising in the eye, while the extranodal marginal zone B-cell lymphoma (EMZL), an indolent often recurrent tumour, occurs most frequently in the ocular adnexal tissue. The two lymphoma subtypes differ significantly in their clinical presentation, subsequent course and outcome as well as in their underlying morphological, immunophenotypical and genetic features. The molecular processes involved in DLBCL and EMZL development are complex, and include chromosomal translocations, mutations caused by aberrant somatic hypermutation, sporadic somatic mutations, and copy number alterations, characterized by deletions and amplifications. These lead to alterations in particular signalling pathways, which in turn activate transcription factors, such as nuclear factor NF-kB. This review provides an overview of the histological features of DLBCL and EMZL, and discusses the current insights into the molecular mechanisms underlying the development of these tumours, when they occur systemically and particularly when they arise in ocular tissues.

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Primary lymphoma of the central nervous system: just DLBCL or not?

Cited by 72 publications

References 32 publications

Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins

Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins

Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma

Molecular pathology of lymphoma

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