Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4916-4925 ◽  
Author(s):  
German Ott ◽  
Marita Ziepert ◽  
Wolfram Klapper ◽  
Heike Horn ◽  
Monika Szczepanowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Molecular Diversity ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Immunohistochemical Markers ◽  
Large B Cell Lymphoma ◽  
Interferon Regulatory Factor 4 ◽  
Large B Cell

Abstract The survival of diffuse large B-cell lymphoma patients varies considerably, reflecting the molecular diversity of tumors. In view of the controversy whether cytologic features, immunohistochemical markers or gene expression signatures may capture this molecular diversity, we investigated which features provide prognostic information in a prospective trial in the R-CHOP treatment era. Within the cohort of DLBCLs patients treated in the RICOVER-60 trial of the German High-Grade Lymphoma Study Group (DSHNHL), we tested the prognostic impact of IB morphology in 949 patients. The expression of immunohistochemical markers CD5, CD10, BCL2, BCL6, human leukocyte antigen (HLA)–DR, interferon regulatory factor-4/multiple myeloma-1 (IRF4/MUM1), and Ki-67 was assessed in 506 patients. Expression of the immunohistochemical markers tested was of modest, if any, prognostic relevance. Moreover, the Hans algorithm using the expression patterns of CD10, BCL6, and interferon regulatory factor-4/multiple myeloma-1 failed to show prognostic significance in the entire cohort as well as in patient subgroups. IB morphology, however, emerged as a robust, significantly adverse prognostic factor in multivariate analysis, and its diagnosis showed a good reproducibility among expert hematopathologists. We conclude, therefore, that IB morphology in DLBCL is likely to capture some of the adverse molecular alterations that are currently not detectable in a routine diagnostic setting, and that its recognition has significant prognostic power.

Multiple Myeloma Oncogene 1 (MUM1)/Interferon Regulatory Factor 4 (IRF4) Upregulates Monokine Induced by Interferon-gamma (MIG) Gene Expression in B-Cell Malignancy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1111-1111
Author(s):  
Shinsuke Iida ◽  
Miyuki Uranishi ◽  
Takaomi Sanda ◽  
Takashi Ishida ◽  
Emi Tajima ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Lines ◽  
Interferon Gamma ◽  
Zinc Finger Protein ◽  
B Cell Lymphoma ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
B Cell Lymphomas ◽  
Interferon Regulatory Factor 4

Abstract MUM1(multiple myeloma oncogene 1)/IRF4(interferon regulatory factor 4) is a transcription regulatory factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas/leukemias and has been reported to predict an unfavorable outcome in some lymphoma subtypes including diffuse large B-cell lymphoma (DLBCL) and B-cell chronic lymphocytic leukemia (B-CLL). To elucidate its role in B-cell malignancies, we prepared stably MUM1-expressing Ba/F3 cells, which proliferated at a higher rate than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the Monokine induced by interferon-gamma (MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1 in inducible MUM1 expressing system. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed in chromatin immunoprecipitation assay. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and its receptor CXCR3 was also coexpressed in B-CLL cell lines that were positive for MUM1. Interestingly, treatment with neutralizing antibodies against MIG and its receptor, CXCR3, partially inhibited the proliferation of two MUM1-expressing B-CLL cell lines. These results suggest that MUM1 plays certain roles in the progression of B-cell lymphomas/leukemias by regulating the expression of various genes including MIG.

scholarly journals A bendamustine resistance gene signature in diffuse large B-cell lymphoma and multiple myeloma

2020 ◽  
Author(s):  
Issa Ismail Issa ◽  
Rasmus Froberg Brøndum ◽  
Hanne Due ◽  
Linnéa Schmidt ◽  
Martin Bøgsted ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Resistance Gene ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Signature ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Introduction to “Immunotherapies for Multiple Myeloma”

2020 ◽  
Vol 13 (11) ◽  
pp. 396
Author(s):  
Massimo Offidani ◽  
Maria Teresa Petrucci
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematological Cancer ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Multiple myeloma (MM) is the second most common hematological cancer after diffuse large B-cell lymphoma, accounting for about 10% of all blood cancers [...]

scholarly journals Immunohistochemical Markers of Tumor Microenvironment as Prognostic Predictors in Diffuse Large B-Cell Lymphoma: Study from an Oncology Centre in South India

2020 ◽  
Author(s):  
Indu R. Nair ◽  
Athulya Sadeesh ◽  
Pooja Phalak ◽  
Pavithran Keechilat
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Chop Regimen ◽  
Immunohistochemical Markers ◽  
Stromal Microenvironment ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction Diffuse large B-cell lymphoma (DLBCL) accounts for 60% of lymphomas in India. Although the survival of DLBCL patients has improved following the addition of rituximab, a subset of patients do not respond well to therapy. Among the several factors responsible for this varied response, tumor microenvironment is considered to be crucial. This study is a search for such prognostic markers in the tumor microenvironment. Materials and Methods A total of 97 patients were selected, of whom 34 were treated with the CHOP regimen and 63 with RCHOP. Immunohistochemistry for CD68 was performed to study the stromal-1 signature and CD34 for stromal-2 signature. Results There was a significant increase in the counts of CD68-positive cells among patients free of events. CD34 count was higher in patients with events in both CHOP and RCHOP groups. Conclusion Additional assessment of stromal microenvironment along with the cell of origin might predict the clinical outcome better in DLBCL.

Primary Low-Grade B-Cell Lymphoma of Skull With Translocation Between Immunoglobulin and Interferon Regulatory Factor 4 Genes

2019 ◽  
Vol 28 (3) ◽  
pp. 330-335
Author(s):  
Mansoor M. Nasim ◽  
David J. Chalif ◽  
Alexis M. Demopoulos ◽  
Judith Brody ◽  
Rova Lee-Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Bone Lesion ◽  
Flow Cytometric Analysis ◽  
B Cell Lymphoma ◽  
Interferon Regulatory Factor ◽  
Low Grade ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 4

Low-grade B-cell lymphoma with immunoglobulin ( IG) and interferon regulatory factor 4 ( IRF4) gene rearrangement is extremely rare, with only 4 cases being previously reported. In this article, we report one additional case that arises from the skull and review the literature. The patient was a 69-year-old man who presented with recurrent and disabling vertigo and was found to have a 5.0 × 1.7 cm lesion within the left posterior parietal bone. Histological examination revealed a bone lesion with diffuse lymphoid infiltrate comprising of mostly small lymphocytes with scant cytoplasm, slightly irregular nuclei and inconspicuous nucleoli, and scattered larger cells resembling prolymphocytes and paraimmunoblasts. Immunohistochemical studies showed that the neoplastic cells were positive for CD20, CD79a, PAX5, CD23, CD43, BCL-2, BCL-6, MUM-1, LEF-1, and IgM and negative for CD5, CD10, cyclinD1, SOX11, and IgD. Flow cytometric analysis identified CD5 negative and CD10 negative monoclonal B cells with lambda light chain restriction. Fluorescence in situ hybridization analysis revealed del(13q) abnormality, but was negative for IGH/BCL2, IGH/CCND1, and BIRC3/MALT1 translocations. Next-generation sequencing identified IGK-IRF4 rearrangement and BRD4 E1113 del abnormalities. Given a low clinical stage (IE) of the disease, the patient did not receive additional treatments and was free of disease at 1 year after the diagnosis.

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