Mature B-Cell Lymphomas, Plasma Cell Neoplasms and Hodgkin Lymphoma: Questions 1–50

B-cell malignancies arise from different stages of B-cell differentiation and constitute a heterogeneous group of cancers including B-cell lymphomas, B-cell leukemias, and plasma cell dyscrasias [...]

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Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage

Virology ◽

10.1016/j.virol.2006.12.016 ◽

2007 ◽

Vol 362 (1) ◽

pp. 179-191 ◽

Cited By ~ 8

Author(s):

Karina Dalsgaard Sørensen ◽

Sandra Kunder ◽

Leticia Quintanilla-Martinez ◽

Jonna Sørensen ◽

Jörg Schmidt ◽

...

Keyword(s):

B Cell ◽

Plasma Cell ◽

Murine Leukemia Virus ◽

Leukemia Virus ◽

B Cell Lymphomas ◽

Cell Stage ◽

Disease Specificity ◽

Murine Leukemia

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Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽

10.1182/asheducation-2013.1.406 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 406-413 ◽

Cited By ~ 9

Author(s):

Michelle Fanale

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Radiation Treatment ◽

Early Stage ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Early Stage Disease ◽

Stage Disease ◽

Relapsed Disease

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.

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Clinical outcomes of composite and sequential B‐cell lymphomas with features intermediate between DLBCL/PMBCL and classical Hodgkin Lymphoma from the SEER database

British Journal of Haematology ◽

10.1111/bjh.16728 ◽

2020 ◽

Vol 190 (3) ◽

pp. 464-466

Author(s):

Velizar Shivarov ◽

Milena Ivanova

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Clinical Outcomes ◽

Seer Database ◽

Classical Hodgkin Lymphoma ◽

B Cell Lymphomas

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Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas

Journal of Personalized Medicine ◽

10.3390/jpm11050355 ◽

2021 ◽

Vol 11 (5) ◽

pp. 355

Author(s):

Ross Salvaris ◽

Jeremy Ong ◽

Gareth P. Gregory

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Treated Patient ◽

Progression Free Survival ◽

Response Rates ◽

Bispecific Antibodies ◽

B Cell Lymphomas ◽

T Cell Therapy ◽

Effector Cells ◽

Non Hodgkin Lymphoma

The treatment landscape of B-cell lymphomas is evolving with the advent of novel agents including immune and cellular therapies. Bispecific antibodies (bsAbs) are molecules that recognise two different antigens and are used to engage effector cells, such as T-cells, to kill malignant B-cells. Several bispecific antibodies have entered early phase clinical development since the approval of the CD19/CD3 bispecific antibody, blinatumomab, for relapsed/refractory acute lymphoblastic leukaemia. Novel bsAbs include CD20/CD3 antibodies that are being investigated in both aggressive and indolent non-Hodgkin lymphoma with encouraging overall response rates including complete remissions. These results are seen even in heavily pre-treated patient populations such as those who have relapsed after chimeric antigen receptor T-cell therapy. Potential toxicities include cytokine release syndrome, neurotoxicity and tumour flare, with a number of strategies existing to mitigate these risks. Here, we review the development of bsAbs, their mechanism of action and the different types of bsAbs and how they differ in structure. We will present the currently available data from clinical trials regarding response rates, progression free survival and outcomes across a range of non-Hodgkin lymphoma subtypes. Finally, we will discuss the key toxicities of bsAbs, their rates and management of these adverse events.

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Activation of the Endoplasmic Reticulum (ER) Unfolded Protein Response (UPR) in Aggressive B-Cell Lymphomas.

Blood ◽

10.1182/blood.v108.11.2038.2038 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2038-2038

Author(s):

Olga Balague ◽

Luis Colomo ◽

Armando Lopez-Guillermo ◽

Elias Campo ◽

Antonio Martinez

Keyword(s):

Endoplasmic Reticulum ◽

Transcription Factors ◽

Western Blot ◽

Er Stress ◽

B Cell ◽

Cell Lines ◽

Plasma Cell ◽

Plasma Cells ◽

Lymphoid Tissues ◽

B Cell Lymphomas

Abstract BACKGROUND The UPR is a prosurvival pathway activated in cells under ER stress induced by the accumulation of unfolded proteins. UPR activation in B cells normally occurs during the differentiation to antibody secreting plasma cells and requires XBP1activation. XBP-1 is a member of the TREB family of transcription factors that exists in the endoplasmic reticulum (ER) as a 33kDa protein, and in the nucleus as an active 50kDa transcription factor. The UPR stimulates two different ER proteins, ATF-6 and Ire-1, to increase XBP-1 transcription and XBP-1 mRNA splicing resulting in the accumulation of the active 50kDa nuclear protein. Moreover XBP1 is a target of proteosome inhibitors and is related to the aggressive behaviour of some carcinomas. The role of the activation of XBP-1 in lymphomas is still unknown. DESIGN: Reactive lymphoid tissues and 25 neoplastic human B-cell lines representing different stages of B-cell development were studied for XBP-1 expression by western blot and XBP-1, PAX-5, Blimp-1/prdm1, MUM-1/IRF-4 and ICSBP1/IRF-8 by immunohistochemistry. XBP-1 activation was assessed in 225 B-cell lymphomas from the archives of the laboratory of pathology by western blot, RT-PCR and immunohistochemistry . To further evaluate whether XBP-1 activation was related to the plasmacytic program or to ER stress signals we analyzed the cell lines by Western blot for XBP-1 and ATF-6 expression. RESULTS We characterize XBP-1 expression in reactive lymphoid tissues, 25 human cell lines and 225 B-cell tumors. In nearly all tonsillar lymphoid cells XBP-1 was detected as a cytoplasmic protein with a paranuclear dot pattern. Nuclear positivity was observed only in scattered centrocytes in the light zone of the germinal centers and in plasma cells, always coexpressed with plasma cell related transcription factors as MUM-1/IRF-4 and Blimp1/prdm1. Active p50XBP-1 was found in 24/25 cell lines by western blot regardless ATF-6 expression and confirmed by immunohistochemistry . Moreover p50XBP1 was found in 27/31(87%) plasmacytomas, 36/64(56%) DLBCL-ABC and in 3/10(30%) DLBCL-GCB and 22/43(51%) plasmablastic lymphomas. Intriguingly, p50XBP1 was detected also in 2/11(18%)BL and 4/25(16%)MCL with blastic features. CONCLUSIONS.XBP-1 is activated in a subset of follicular centre cells committed to plasma cell differentiation and in plasma cells.UPR prosurvival pathways in the neoplastic cell lines are activated independently of the extent of the ATF-6 activation.p50XBP1 is mostly activated in aggressive B-cell lymphomas regardless to the plasmacytic differentiation of the tumours. Thus, p50XBP-1 may be a new molecular target in the treatment of aggressive B-cell malignancies.

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Aberrant Expression of Golgin-84 in Non-Hodgkin Lymphomas and Plasma Cell Myeloma

Blood ◽

10.1182/blood.v118.21.4633.4633 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4633-4633

Author(s):

Ling Chen ◽

Yaling Yang ◽

C. Cameron Yin ◽

Gary Lu ◽

Su Chen ◽

...

Keyword(s):

Lymph Nodes ◽

B Cell ◽

Hodgkin Lymphoma ◽

Plasma Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoid Cells ◽

Plasma Cell Myeloma ◽

Expression Levels ◽

Non Hodgkin Lymphoma

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

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