Germinal center B-cell-like diffuse Large B-cell Lymphoma (GCB) DLBCL

2017-09-01   Samir Dalia , Luis Miguel Juárez Salcedo 

1.Principe de Asturias University Hospital, Madrid, Spain; Dr.luisjuarez@gmail.com (LMJC); Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA; sdalia@gmail.com (SD)

Abstract

Review on Germinal center B-cell-like diffuse Large B-cell Lymphoma (GCB) DLBCL, with data on clinics, and genes.

Clinics and Pathology

Disease

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% to 40% of all non-Hodgkin lymphoma (NHL) cases. (Sujobert P, et al., 2016) Gene expression profiling (GEP) studies have identified ≥ 2 distinct molecular subtypes, termed germinal center B-cell (GCB) and activated B-cell (ABC), which are believed to represent lymphomas arising from different stages of lymphoid differentiation. (Alizadeh AA, et al., 2000; Rosenwald A, et al., 2002) The GCB DLBCL represent approximately 50% of DLBCL. (Karmali R, et al., 2017).
GCB DLBCLs are thought to arise from normal germinal center B cells and show features that are consistent with germinal center B cell derivation. (Alizadeh AA, et al., 2000; Rosenwald A, et al., 2002) These harbor oncogenetic hits typical such as t(14:18) translocation, the mutations of epigenetic modifiers ( EZH2, KMT2D) or mutations in the genes encoding the S1PR2 receptor or its signal transduction protein GNA13. (Sehn L, et al., 2015)
This subtype has a cure rate of about 70 to 80% with currently available immune chemotherapy regimens like R-CHOP, R-DHAP, R-ICE or DA-EPOCH-R. (Thieblemont C, et al., 2011; Delarue R, et al., 2013; Cunningham D, et al., 2013)

Etiology

GCB DLBCLs are believed to derived from lymphoid cells residing in the germinal center and therefore express genes normally detected in germinal center B cells, such as CD10, LMO2 and the transcriptional repressor Bcl6. (Béguelin W, et al., 2013; Sujobert P, et al., 2016; Lenz G et al. 2008) Approximately 30% to 40% of GCB DLBCLs have a t(14:18) translocation, 30% have REL amplifications, 20% have mutations of the histone methyltransferase EZH2 and 10% have a deletion of the PTEN, all of which are virtually never seen in ABC DLBCL. (Pfeifer M, et al., 2013; Morin RD, et al., 2011; Pasqualucci L, et al., 2011)

Epidemiology

The median age is 70 years old (occur in children and adults). The incidence is between 25-30% of adult NHLs (western countries), with slight male predominance.

Pathology

GC-DLBCL is described as CD-10 positive, Bcl-6 positive and MUM-1 negative. (Sujobert P, et al., 2016)

Treatment

It is the most curable subtype, with a 5-year overall survival (OS) rate of nearly 75%. The GC subtype has a cure rate of about 70 to 80% with currently available therapies. The infusional regimen of dose-adjusted etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (DA-EPOCH-R) or Hyper CVAD-R, have yield promising results especially in the GC- DLBCL subtype. (Petrich AM, et al., 2014) Similarly, R-CHOP, R-DHAP and R-ICE could be valuable options of treatment. (Delarue R, et al., 2013; Cunningham D, et al., 2013). In the new era of targeted therapy, it could soon benefit from inhibitors of the EZH2, Bcl-2 and Bcl-6 oncoproteins.

Note

GC-DLBCL largely express gene products, such as Bcl-6, GCSAM (HGAL) and LMO2 that define normal germinal center B cells within the germinal center light zone. (Alizadeh AA, et al., 2000; Rosenwald A, et al., 2002) Malignant GC-DLBCL clones continue to undergo somatic hypermutation of their variable immunoglobulin heavy chain gene and have often switched IgH classes that are mediated by AID, an enzyme that is characteristically expressed at high levels in germinal center B cells. (Lossos IS, et al., 2000) The GC-DLBCL subtype is characterized by low level of NF-kB activation and its survival is not dependent on NF-kB. (Davis RE, et al., 2001; Dal Porto JM, et al., 2004)
Translocation of BCL2and/or MYC genes, are commonly observed in GC-DLBCL. These translocation lead to constitutive activation of c-MYC and the anti-apoptotic Bcl-2 protein and to a malignant transformation by preventing terminal differentiation or blocking apoptosis. (Shaffer 3rd AL, et al., 2012) 20% have gain of function mutations of the histone methyltransferase EZH2, which is a master regulator of the GC-DLBCL phenotype and cooperates, partly with Bcl-2 and BCL6 to mediate lymphomagenesis. Is also characterized by downregulation of the phosphatase and tensin homologue (PTEN) and concomitant upregulation of phosphatidylinositol-3-kinase (PI3K) signaling pathway. (Sehn L, et al., 2015)

Highly cited references

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Bibliography

Pubmed IDLast YearTitleAuthors
106769512000Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.Alizadeh AA et al
236801502013EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation.Béguelin W et al
236154612013Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles.Cunningham D et al
117482862001Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells.Davis RE et al
235787222013Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial.Delarue R et al
282293642017Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy.Karmali R et al
250605882014MYC-associated and double-hit lymphomas: a review of pathobiology, prognosis, and therapeutic approaches.Petrich AM et al
240915352013PI3K/AKT addiction in subsets of diffuse large B-cell lymphoma.Pfeifer M et al
120750542002The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.Rosenwald A et al
254994482015Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity.Sehn LH et al
222247672012Pathogenesis of human B cell lymphomas.Shaffer AL 3rd et al
278888732016Molecular Classification of Diffuse Large B-cell Lymphoma: What Is Clinically Relevant?Sujobert P et al
219478242011The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study.Thieblemont C et al

Citation

Samir Dalia ; Luis Miguel Juárez Salcedo

Germinal center B-cell-like diffuse Large B-cell Lymphoma (GCB) DLBCL

Atlas Genet Cytogenet Oncol Haematol. 2017-09-01

Online version: http://atlasgeneticsoncology.org/haematological/2147/germinal-center-b-cell-like-diffuse-large-b-cell-lymphoma-(gcb)-dlbcl

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