Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC , BCL-2 , and BCL-6

Li, Xiaomei; Huang, Ying; Bi, Chengfeng; He, Hong; Zhang, Hong; Yu, Qiu Bo; Fu, Kai; Li, Dan

doi:10.1016/j.prp.2017.02.012

Cited by 9 publications

(13 citation statements)

References 37 publications

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“…Further studies will be necessary to further investigate these hypotheses. Interestingly TOX mutations were also found in primary central nervous system lymphoma (PCNSL), another large B-cell lymphoma type with an ABC phenotype [31,32], where they have been found to be associated with shorter overall survival [33].…”

Section: Fig 4 Expression Of Tox In Normal Lymphoid Tissues (A)mentioning

confidence: 99%

High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations

Maestre¹,

García-García

Jiménez³

et al. 2020

PLoS ONE

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Thymocyte selection-associated high-mobility group box (TOX) is a DNA-binding factor that is able to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. TOX has multiple roles in the development of the adaptive immune system including development of CD4 T cells, NK cells and lymph node organogenesis. However very few antibodies recognizing this molecule have been reported and no extensive study of the expression of TOX in reactive and neoplastic lymphoid tissue has been performed to date. In the present study, we have investigated TOX expression in normal and neoplastic lymphoid tissues using a novel rat monoclonal antibody that recognizes its target molecule in paraffin-embedded tissue sections. A large series of normal tissues and Band T-cell lymphomas was studied, using whole sections and tissue microarrays. We found that the majority of precursor B/T lymphoblastic, follicular and diffuse large B-cell lymphomas, nodular lymphocyte-predominant Hodgkin lymphomas and angioimmunoblastic T-cell lymphomas strongly expressed the TOX protein. Burkitt and mantle cell lymphomas showed TOX expression in a small percentage of cases. TOX was not found in the majority of chronic lymphocytic leukemia, myelomas, marginal zone lymphomas and classical Hodgkin lymphomas. In conclusion, we describe for the first time the expression of TOX in normal and neoplastic lymphoid tissues. The co-expression of TOX and PD-1 identified in normal and neoplastic T cells is consistent with recent studies identifying TOX as a critical regulator of T-cell exhaustion and a potential immunotherapy target. Its differential expression may be of diagnostic relevance in the differential diagnosis of follicular lymphoma, the identification of the phenotype of diffuse large B-cell lymphoma and the recognition of peripheral T-cell lymphoma with a follicular helper T phenotype.

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Section: Fig 4 Expression Of Tox In Normal Lymphoid Tissues (A)mentioning

confidence: 99%

High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations

Maestre¹,

García-García

Jiménez³

et al. 2020

PLoS ONE

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“…Primary CNS lymphoma (PCNSL) is a rare, highly aggressive extranodal subtype of non-Hodgkin's lymphoma originating in the brain, spinal cord, eyes, or leptomeninges [1,2]. PCNSL may represent 12-15% of lymphomas in HIV-AIDS, but only 1% of all lymphomas in the general population, and 4% of intracranial tumors in immunocompetent patients [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

“…PCNSL is classified histologically as diffuse large B-cell lymphoma (DLBCL) in 90-95% of cases, despite arising in the brain, which does not contain conventional lymphoid tissue [1-3, 6, 7]. The 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tissues considered PCNSL a distinct new subtype of DLBCL, characterized as an aggressive high-grade B-cell neoplasm with a poorer prognosis than its systemic counterpart [2,7].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus-Positive Primary Central Nervous System Lymphoma in a 40-Year-Old Immunocompetent Patient

Hajtovic

Liu

Diefenbach

et al. 2021

Cureus

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Epstein-Barr virus-positive (EBV+) primary central nervous system lymphoma (PCNSL) is a clinical entity rarely reported in young immunocompetent patients. Here, we present the case of a 40-year-old female with no history of immunosuppression or immunodeficiency, who presented with a ring-enhancing lesion in the right basal ganglia. The tumor generated significant vasogenic edema and mass effect, causing midline shift, symptoms of increased intracranial pressure, and rapidly progressive neurologic dysfunction. She underwent gross total resection of the tumor through a tubular retractor. Her tumor was of the diffuse large B cell lymphoma (DLBCL) subtype of PCNSL and was positive for EBV. No immunodeficiency or extracranial disease was identified. After adjuvant therapy with high-dose methotrexate, rituximab, and temozolomide, she remains disease-free two years after initial presentation. EBV+ PCNSL, although rare in young immunocompetent adults, poses unique clinical challenges and may require surgical intervention in the acute setting in some cases.

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“…In this regard, questions remain as to whether PVRL and PCNSL are synonymous or subtypes that could be further differentiated by their molecular signatures. While the ABC DLBCL subtype is widely recognized in both PCNSL and VRL (Camilleri-Broet et al, 2006;Cheng et al, 2008;Montesinos-Rongen et al, 2009;Hattab et al, 2010;Li et al, 2017;Belhouachi et al, 2020), many have independently reported the detection of GCB DLBCL in PCNSL and VRL (Bhagavathi and Wilson, 2008;Montesinos-Rongen et al, 2008;Wang, 2017;Arai et al, 2020), adding discordance to our current understanding. Admittedly, the classification of DLBCL based on gene expression profiling (Alizadeh et al, 2000) and IHC (Hans's algorithm) (Hans et al, 2004) was developed almost two decades ago; more importantly, they were not formulated to classify immune-privileged lymphomas such as PCNSL or VRL.…”

Section: Discussionmentioning

confidence: 96%

“…In a landmark publication in 2000, Alizadeh et al (2000) used gene expression profiling to identify three DLBCL molecular subtypes, namely, activated B-like DLBCL (ABC), germinal center B-cell (GCB), and primary mediastinal DLBCL. Based on this stratification according to molecular signatures, PCNSL was subsequently classified as ABC DLBCL (Camilleri-Broet et al, 2006;Cheng et al, 2008;Montesinos-Rongen et al, 2009;Hattab et al, 2010;Li et al, 2017;Belhouachi et al, 2020). Indeed, >80% of VRL cases belong to this subtype (Araujo and Coupland, 2017;Karakawa et al, 2018;Chen et al, 2019;Fan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC , BCL-2 , and BCL-6

Cited by 9 publications

References 37 publications

High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations

High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations

Epstein-Barr Virus-Positive Primary Central Nervous System Lymphoma in a 40-Year-Old Immunocompetent Patient

Table_1.DOCX

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