Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 706-710 ◽  
Author(s):  
Iwona Wlodarska ◽  
Peet Nooyen ◽  
Brigitte Maes ◽  
José I. Martı́n-Subero ◽  
Reiner Siebert ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Hodgkin Lymphoma ◽  
Germinal Center ◽  
Classical Hodgkin Lymphoma ◽  
Germinal Center B Cell

We studied the genomic status of BCL6 in 23 cases of nodular lymphocyte predominance Hodgkin lymphoma (NLPHL) and 40 cases of classical Hodgkin lymphoma (cHL), using dual-color interphase fluorescence in situ hybridization (FISH). The BCL6rearrangement was identified in 48% of NLPHL cases and was not detected in cHL cases. As a confirmation, sequential or simultaneous immunohistochemistry (IHC) and FISH using CD20 or BCL6 antibodies and BCL6 DNA probes was performed in 8 NLPHL cases. The BCL6-associated translocations, t(3;22)(q27;q11), t(3;7)(q27;p12), and the most probable t(3;9)(q27;p13), were identified in 3 cases. A consistent expression of BCL6 protein in popcorn cells with the highest number of intensely stained cells in cases with a genomic BCL6rearrangement was shown by IHC. These findings support the hypothesis of a germinal center B cell–derived origin of NLPHL, indicate a significant role of BCL6 in the pathogenesis of NLPHL, and provide further evidence of the genetic diversity underlying the pathogenesis of NLPHL and cHL.

Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B-cell-derived mantle cell lymphoma

2013 ◽  
Vol 134 (4) ◽  
pp. 832-843 ◽  
Author(s):  
Stefanie Schneider ◽  
Barbara Crescenzi ◽  
Markus Schneider ◽  
Stefano Ascani ◽  
Sylvia Hartmann ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Classical Hodgkin Lymphoma ◽  
Germinal Center B Cell ◽  
Mantle Cell

Immuno–Fluorescence In Situ Hybridization Index Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A GELA Study

2009 ◽  
Vol 27 (33) ◽  
pp. 5573-5579 ◽  
Author(s):  
Christiane Copie-Bergman ◽  
Philippe Gaulard ◽  
Karen Leroy ◽  
Josette Briere ◽  
Maryse Baia ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immunohistochemical Markers ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients and Methods Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray. Results LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis. Conclusion Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.

Fluorescence in situ hybridization assessment of the telomeric regions of jumping translocations in a case of aggressive B-cell non-Hodgkin lymphoma

1997 ◽  
Vol 98 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Brian A. Gray ◽  
Angela Bent-Williams ◽  
Julie Wadsworth ◽  
Russell L. Maiese ◽  
Andres Bhatia ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma

Immunohistochemical Profile and Fluorescence In Situ Hybridization Analysis of Diffuse Large B-Cell Lymphoma in Northern China

2010 ◽  
Vol 134 (5) ◽  
pp. 759-765
Author(s):  
Ting Li ◽  
L. Jeffrey Medeiros ◽  
Pei Lin ◽  
Hongfang Yin ◽  
Martin Littlejohn ◽  
...  
Keyword(s):  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Northern China ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Abstract Context.—Gene expression profiling of diffuse large B-cell lymphoma using complementary DNA microarrays has revealed 2 major prognostic groups in Western countries: germinal center B-cell–like and nongerminal center B-cell–like lymphomas. Immunohistochemical analysis using antibodies specific for CD10, BCL6, and MUM1 has been proposed as a surrogate for gene expression profiling. Objective.—To study the immunohistochemical features of diffuse large B-cell lymphoma cases from northern China because geographic differences for this disease are known to exist. Design.—Morphologic, immunohistochemical, and fluorescence in situ hybridization analyses of 63 cases of diffuse large B-cell lymphoma from northern China. Results.—There were 38 men and 25 women with a median age of 57 years (range, 12–87 years). CD10 was positive in 19 cases (30%), BCL6 was positive in 22 cases (35%), and MUM1 was positive in 32 cases (51%). Twenty-one (33%) cases were germinal center B-cell–like lymphoma, and 42 (67%) were nongerminal center B-cell–like lymphoma. BCL2 was expressed more often in nongerminal center B-cell–like disease versus germinal center B-cell–like disease (60% versus 24%, P  =  .01) and in nodal versus extranodal (64% versus 30%, P  =  .01) cases. Fluorescence in situ hybridization analysis showed BCL6, MYC, and BCL2 rearrangements in 11 of 32 (34%), 8 of 27 (30%), and 11 of 50 (22%) cases, respectively. Conclusions.—These results add to what is known about the geographic variation of diffuse large B-cell lymphomas. In northern China, the frequency of the germinal center B-cell–like type and BCL6 expression and/or BCL6 rearrangement is less and the frequency of MYC rearrangement is greater than have been reported in Western countries.

scholarly journals Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ting-ting Zhang ◽  
David G Gonzalez ◽  
Christine M Cote ◽  
Steven M Kerfoot ◽  
Shaoli Deng ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
B Cell Differentiation ◽  
B Cell Maturation ◽  
Germinal Center B Cell ◽  
T Cell Help ◽  
Dose Dependent

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

scholarly journals A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 204 ◽  
Author(s):  
Sakai ◽  
Rezano ◽  
Okada ◽  
Ohtsuki ◽  
Kawashima ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Germinal Center ◽  
Lymphoid Tumor ◽  
Germinal Center B Cell ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Factor Α

Hodgkin lymphoma (HL) is one of the most difficult neoplasms in terms of cytopathological research owing to the lack of established cytological murine models. Although HL is believed to be of lymphoid germinal center B-cell origin, HL cells exhibit unique biphenotypic characteristics of B cells and macrophages. B-cell/macrophage biphenotypic cells have also been identified in the spleen of Lyn-deficient mice. Moreover, Lyn-targeting germinal center-associated nuclear protein (GANP)-transgenic mice (Ig-ganpTg mice) spontaneously develop a lymphoid tumor. We aimed to investigate whether the lymphoid tumor developed in Ig-ganpTg mice exhibit biphenotypic characteristics of B cells/macrophages that correspond to human HL. Here, we demonstrated GANP overexpression in human HL cells and found that it may regulate transdifferentiation between B cells and macrophages. We also demonstrated that tumors were comparable with B-cell/macrophage biphenotypic Hodgkinoid lymphomas. The tumor cells expressed macrophage-related F4/80, CD68, and CD204 as well as cytoplasmic B220 and µ-/κ-chains; in addition, these cells exhibited phagocytic activity. These cells also expressed transcripts of CD30; c-fms; and the cytokines monocyte chemoattractant protein (MCP)-1, MCP-5, RANTES, tumor necrosis factor-α and thrombopoietin associated with macrophages as well as granulocyte/macrophage colony-stimulating factor, interleukin (IL)-4, IL-10, IL-12, and IL-13. Ig-ganpTg mice represent a novel cytological model for the study of cytopathological etiology and oncogenesis of HL.

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