Diffuse large B-cell lymphoma (DLBCL) (2023)

Request forms


  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:Cytomorphology
  • Anticoagulant:EDTA
  • Recommendation:obligatory
  • Method:Immunophenotyping
  • Anticoagulant:EDTA or Heparin
  • Recommendation:obligatory
  • Method:Chromosome analysis
  • Anticoagulant:Heparin
  • Recommendation:facultative
  • Method:FISH
  • Anticoagulant:EDTA or Heparin
  • Recommendation:obligatory
  • Method:Molecular genetics
  • Anticoagulant:EDTA or Heparin
  • Recommendation:facultative
  • Classification
  • Subclassification
  • Diagnostic methods
  • Pathogenesis
  • Prognosis
  • Therapy

Diffuse large B-cell lymphoma not otherwise specified(DLBCL, NOS) is the most common malignant lymphoma andconstitutes 25-35% of adult non-Hodgkin lymphomas. The median age of onset of this aggressive neoplasm is 70-80 years, but it can also occur in children and young adults. Usually DLBCL arises de novo, but can also represent transformation of a less aggressive lymphoma (Swerdlow et al. 2017). In the case of transformation from chronic lymphocytic leukemia to DLBCL, this is referred to as Richter transformation or Richter syndrome (Rossi et al. 2018).

DLBCL: Classification

Diffuse large B-cell lymphomas are classified as mature B-cell neoplasms according to the WHO classification (2017); in addition to DLBCL, NOS, other subtypes of DLBCL are known:

  • primary diffuse large B-cell lymphoma of the central nervous system
  • primary cutaneous diffuse large B-cell lymphoma, leg type
  • EBV-positive diffuse large B-cell lymphoma, NOS
  • diffuse large B-cell lymphoma associated with chronic inflammation
  • fibrin associated diffuse large B cell lymphomaHHV8-positive diffuse large B-cell lymphoma

Subclassification of DLBCL

Based on morphology, DLBCL, NOS can be subdivided into: centroblastic, immunoblastic, anaplastic and other rare variants. However, the most important classification for DLBCL is the subtyping according to the cell of origin (COO). The neoplastic cells can originate from the germinal centre (germinal centre B cells, GCB) or the cells have already passed the germinal centre (post GCB or activated B cells, ABC(Basso et al. 2015, Chapuy et al. 2018). In accordance with the respective cell of origin, persistent somatic hypermutation can be detected in GCB-DLBCL, whereas this has already been completed in ABC-DLBCL.

In addition to somatic hypermutation, the processes of B-cell selection, class switching and terminal differentiation also take place in the germinal centre. All these steps are regulated by a finely tuned gene expression programme. For example, the transcriptional repressor BCL6 is expressed exclusively in the germinal centre (Basso et al. 2015). BCL6 suppresses cell cycle arrest as well as DNA damage recognition and repair. BCL6-mediated suppression of the proliferation factor MYC and the anti-apoptotic factor BCL2 (and other apoptosis factors) prevents uncontrolled proliferation in the germinal centre and maintains a pro-apoptotic state (Pasqualucci et al. 2018, Basso et al. 2010, Ci et al. 2009). Deregulation of these three genes, BCL6, BCL2 and MYC, contributes significantly to the pathogenesis of DLBCL.

Due to the prognostic relevance, the COO subtype of the disease should already be determined at diagnosis. The gold standard here would be gene expression analysis, but this is not used comprehensively in routine practice. However, 10-15% of cases cannot be assigned to a COO subtype (DLBCL, NOS unclassified) (Alizadeh et al. 2000, Rosenwald et al. 2002, Wright et al. 2003, Scott et al. 2015). Instead of gene expression analysis, mainly immunohistochemical approaches are used for subtype determination, e.g. the Hans algorithm checks the expression of the antigens IRF4/MUM1, CD10 and BCL6 and classifies cases into GCB and non-GCB (contains ABC-DLBCL and DLBCL, unclassified) (Hans et al. 2004). However, a meta-analysis showed that the classification according to immunohistochemical algorithms has no significant prognostic value (Read et al. 2014).

The two subtypes also differ in their tumour biology: a chronic, (auto)antigen-dependent activation of the B-cell receptor signalling pathway is characteristic for ABC-DLBCL (Davis et al. 2010). This also results in a constitutive activation of the downstream NF-kB signalling pathway, which is necessary for neoplastic cell survival in ABC-DLBCL. In contrast, neoplastic cells of the GCB subtype are dependent on tonic activation of the B-cell receptor. This weak, antigen-independent activation of B-cell receptor signalling is also normal-physiologically essential for B-cell survival. In both healthy and neoplastic cells, downstream signal transduction occurs via activation of the PI3K/AKT pathway (Chen et al. 2008, Efremov 2016, Myers et al. 2017). The GCB subtype therefore shows no dependence on the NF-kB signalling pathway (Efremov 2016).

Genetic characterisation of DLBCL is of increasing importance. Only 85-90% of DLBCL cases can be classified via the subtype determined by gene expression analysis. Using molecular genetic subclassification, this proportion can be significantly increased to 93.4% (Schmitz et al. 2018) and 96% (Chapuy et al. 2018) in two recent studies. In the study by Schmitz et al. DLBCL cases are classified into four genetically-defined groups as well as two groups defined by the COO subtype (other ABC and other GCB) and the unclassifiable cases (6.6%). In the study by Chapuy et al. cases are classified into a total of five clusters, 12 of 302 cases were unclassifiable. In both studies, the identified clusters/subgroups had prognostic relevance and overall allowed for a more refined risk stratification than the COO subclassification.


In the diagnostics of lymphoma, the cytomorphology and in particular the histology are important for guiding the downstream diagnostics. In addition, blood and bone marrow smears can be used to assess blood lymphocytosis (rare in this lymphoma entity).

The neoplastic cells typically express pan-B cell markers (CD19+, CD20+, CD22+, CD79a+, PAX5+), but may lack one or more of these. The majority of DLBCL, NOS cases show expression of membrane-bound and cytosolic immunoglobulin (most commonly IgM, less frequently IgG and IgA). The antigen CD10, which is also checked in context of immunohistological subtype differentiation (Hans algorithm), is expressed in 30-50% of cases. CD138 is rarely coexpressed, CD30 is positive in only 10-20%. In EBV+ DLBCL, this marker is usually positive. Only 5-10% of DLBCL, NOS are positive for CD5, there is a strong association with de novo DLBCL. Since DLBCL rarely leads to lymphoma spread, immunohistochemistry of the lymph node biopsy is particularly useful for determining the immunophenotype.

Chromosome analysis can detect rearrangements, gains/amplifications and losses in both subtypes. For example, while MYC rearrangements occur with similar frequency in both subtypes, many cytogenetic abnormalities show an association with one subtype. Table 1 lists recurrent chromosomal alterations and their frequencies in the two DLBCL subtypes.

Table 1:Recurrent and subtype-associated cytogenetic alterations in DLBCL according toWHO (2017)






e.g. t(14;18)(q32;q21.3)

< 5%





MYC, single hit - without further rearrangements of BCL2 and/or BCL6,
many possible translocation partners, mostly IG loci



Ligands of PD1

very rare

very rare


very rare

very rare




Copy-number aberrations

Gain / amplification

2p16 (REL)






9p24.1 (CD274/PDCD1LG2)



18q21.3 (BCL2)




1p36.32 (TNFRSF14)



6q21 (PRDM1)



9p21 (CDKN2A)



In DLBCL, the method of fluorescence in situ hybridisation is suitable for detecting rearrangements, especially at interphase nuclei. Table 1 lists the most common chromosomal abnormalities in DLBCL, some of which can also be detected by FISH. Furthermore, FISH can be used to exclude the presence of HGBL (simultaneous rearrangement of MYC and BCL2 and/or BCL6). In addition, FISH can be used to clarify or validate complex chromosomal alterations by means of chromosome painting or 24-colour FISH in addition to the classical metaphase analysis. Due to the rare lymphoma outgrowth in DLBCL, a lymph node biopsy is usually available as starting material. In this case, fluorescence in situ hybridisation performed on formalin-fixed and paraffin-embedded tissue is reproducible and significantly supports diagnosis and differential diagnosis (Barth et al. 2013, Ventura et al. 2006, Foot et al. 2011).

Mutations in chromatin-modifying enzymes (ARID1A, TET2), lysine methyltransferases (KMT2C and KMT2D), the acetyltransferases CREBBP and EP300, and the TP53 and MEF2B genes are recurrently mutated in both ABC and GCB-DLBCL. However, aberrations of the lysine methyl and acetyltransferases are more frequently found in GCB-DLBCL (Pasqualucci et al. 2018). Immune evasive phenotypes (see pathogenesis) can also occur in both subtypes. MYD88 mutations are strongly associated with the ABC subtype, but can also occur in rare cases in GCB-DLBCL, with the MYD88 L265P mutation being almost exclusive to the ABC subtype (Pasqualucci et al. 2018, Karube et al. 2018). Recurrent mutations and their frequencies in each subtype are listed in Table 2.

Table 2:Recurrent mutations in DLBCL according to WHO (2017), mutation frequencies for FOXO1 taken from (Karube et al. 2018)





Epigenetic factors


very rare










very rare


Tumor suppressor




Immune evasion







Signal transduction


very rare


















very rare


Terminal differentiation



very rare

Transcription factors







DLBCL: Pathogenesis

BCL2 expression

Aberrant expression of the anti-apoptotic molecule BCL2 occurs in both subtypes. However, the underlying genetic abnormalities differ for the two subtypes. While BCL2 translocations, such as t(14;18)(q32;q21.3), are detected in up to 40% of cases in the GCB subtype, BCL2 translocations are rare in the ABC subtype (Iqbal et al. 2004). Nevertheless, approximately 60% of patients with ABC-DLBCL show high BCL2 levels (Hu et al. 2013). Contributing factors are gains/amplifications of the locus (depending on the study, up to more than 55% of ABC-DLBCL cases) as well as aberrations that activate the NF-kB signalling pathway and thus lead to increased BCL2 expression (Iqbal et al. 2006, Iqbal et al. 2011, Davis et al. 2001).

BCL6 deregulation

Up to 35% of patients have genetic abnormalities of the BCL6 gene. In 1/3 of cases, translocations are the cause of aberrant BCL6 expression, here more frequently in the ABC subtype than in the GCB subtype (2:1) (Pasqualucci et al. 2018). Over 20 possible partner loci are known for the translocation leading to promoter substitution, with IG heavy- or light-chain loci most commonly involved in the rearrangement. Somatic BCL6 mutations also occur with high frequency; due to regulatory elements, the first 2 kb downstream of the transcription start site in particular represent a hotspot for mutations (75% of BCL6 mutations). A variety of indirect mechanisms also contribute to BCL6 downregulation (Pasqualucci et al. 2018).

MYC expression

Expression of the transcription factor MYC is associated with a proliferative phenotype (high Ki-67 proliferation index). In 10-14% of GCB-DLBCL cases, ectopic and constitutive MYC expression occurs, frequently caused by translocations with different partner loci, often involving IG loci (IGH, IGK, IGL) (Pasqualucci et al. 2018, Swerdlow et al. 2017).

If translocations of MYC and BCL2 and/or BCL6 occur simultaneously, these are referred to as double-hit or triple-hit lymphomas, respectively; according to the current WHO classification (2017), these are to be classified as "Highly malignant B-cell lymphomas (HGBL) with gene rearrangements". It is estimated that 3-10% of DLBCL patients have double- or triple-hit lymphoma (Rosenthal et al. 2017), a recent study (Scott et al. 2018) counts the proportion of HGBL in a cohort of 1228 DLBCL patients at 7.9%. HGBL occurred mainly in the GCB subtype and accounted for 13.3% of GCB-DLBCL cases, while the proportion of HGBL cases in ABC-DLBCL was 1.7% (Scott et al. 2018).

The so-called double-expressing phenotype, which shows co-expression of the MYC and BCL2 proteins, must be distinguished. According to WHO recommendations, such a phenotype is present if the MYC protein is detectable in more than 40% of the cells and the BCL2 protein in more than 50% of the cells in the immunohistochemical analyses. In many cases, no underlying chromosomal abnormalities is detectable. Double-expressing lymphomas are associated with the ABC subtype and a worse prognosis (Swerdlow et al. 2016, Pasqualucci et al. 2018).

Immune evasion

DLBCL is characterised by the absence of class I (60%) or class II (40-50%) MHC molecules (Pasqualucci et al. 2018). The variety of mechanisms underlying the lack of expression of MHC molecules include point mutations or losses of HLA loci (e.g. del(6p21.3)), epigenetic silencing, CD58 mutations, inactivating mutations of CIITA, and aberrations of the B2M gene (Pasqualucci et al. 2018). Overexpression of ligands of the programmed death 1 (PD1) factor can also contribute to the immunovascular phenotype. This is caused by copy number gains of the 9p24 region or, more rarely, translocations of PD1 ligands (Chapuy et al. 2016). Overexpression leads to reduced infiltration of cytotoxic T cells into the tumour tissue and a worsening of the prognosis (Rimsza et al. 2006, Rimsza et al. 2004).

Prognosis in DLBCL

The classification of DLBCL according to COO subtypes is of great relevance for the prognosis as well as a possible therapy, as the two subtypes differ significantly in their response to the R-CHOP regime (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). The prognosis in GCB-DLBCL (with a 5-year survival of approx. 80%) is better than in ABC-DLBCL (5-year survival of approx. 50%) (Pon et al. 2016). Clinical parameters also have a prognostic influence. The "International Prognostic Index (IPI)" takes into account the patient's age, the lactate dehydrogenase level in the blood, the number of extranodal cases, the general condition of the patient, determined according to criteria of the ECOG (Eastern Cooperative Oncology Group), as well as the staging of the lymphoma according to the Ann Arbor classification. Stratification into four risk groups is based on the IPI risk score.

Several studies have shown an association of a less favourable prognosis and BCL2 gains in DLBCL and BCL2 translocations or BCL2 expression in GCB-DLBCL specifically (Barrans et al. 2003, Iqbal et al. 2011, Visco et al. 2013, Lu et al. 2015, Chapuy et al. 2018). Translocations of MYC have also been associated with worsening prognosis in some studies (Barrans et al. 2010, Copie-Bergman et al. 2015, Savage et al. 2009, Tzankov et al. 2014, Chapuy et al. 2018). Data on the prognostic significance of BCL6 translocation and MYC gain/amplification is inconsistent (Barrans et al. 2002, Iqbal et al. 2007, Shustik et al. 2010, Lu et al. 2015, Stasik et al. 2010, Testoni et al. 2011, Valentino et al. 2013, Yoon et al. 2008). Independent of genetic aberrations, simultaneous expression of MYC and BCL2 (so-called double-expressing lymphomas) is associated with an unfavourable prognosis (Swerdlow et al. 2016, Pasqualucci et al. 2018).

Mutations with a negative prognostic impact include mutations of the transcription factor FOXO1 (Trinh et al. 2013). TP53 losses/mutations are also associated with an unfavourable prognosis (Xu-Monette et al. 2012, Young et al. 2008), as are losses of the CDKN2A locus (Jardin et al. 2010), although Karube et al. demonstrated an independent prognostic effect only in the case of co-aberrations of both loci (Karube et al. 2018). In the same study, mutations in the KLHL6 and SGK1 genes were also negative prognostic indicators, independent of COO subtype and IPI score. When signalling pathways were considered, aberrations in the NOTCH pathway had a negative prognostic impact and alterations in the JAK-STAT pathway had a favourable prognostic impact (Karube et al. 2018).

Karube et al. also associate chromosomal alterations (gains in 5p15, 11q24, 12q14 as well as 12q15 and losses in 8q12) with a reduced rate of complete remission (Karube et al. 2018). Chapuy et al. demonstrated in another study that gains in 13q31.2/miR-17-92 and 18p and loss of 1q24.12 were associated with reduced progression-free and/or overall survival (Chapuy et al. 2018).

Diffuse large B-cell lymphoma prognosis calculation:

Hier gelangen Sie zur Prognoseberechnung des R-IPI-Scores.

Click here for the prognosis calculation of the R-IPI score.

Therapy for DLBCL

The R-CHOP regimen is currently the gold standard in the treatment of DLBCL, NOS. However, ABC DLBCL cases respond significantly worse to treatment with R-CHOP. Currently, however, the COO subtype does not influence treatment decisions (outside of trials) because the diagnostics required for this cannot be offered nationwide. With the knowledge of similarities and differences between the two subtypes, targeted therapies could possibly be used in the future to improve the treatment of DLBCL, NOS.

Potential targeted therapies for:

The high frequency of aberrations of BCL2 and BCL6 make them suitable therapeutic targets for inhibitors in both subtypes (Pon et al. 2016, Pasqualucci et al. 2018). While inhibition of BCL6 is the subject of preclinical research (Cerchietti et al. 2009, Cerchietti et al. 2010), results of initial phase I studies on the BCL2 inhibitor venetoclax are already available for use in refractory/relapsed non-Hodgkin's lymphoma (NHL). The DLBCL group showed the lowest overall response within the NHL patient groups. This was the case with venetoclax monotherapy (overall response of 18% compared to 75% in patients with mantle cell lymphoma) (Davids et al. 2017) and also in combined administration with bendamustine and rituximab (de Vos et al. 2018). Here, the overall response of 41% was significantly higher than for monotherapy, but significantly lower than the overall response of 75% in patients with follicular lymphoma or 100% in patients with mantle cell lymphoma (6 of 6 patients) (de Vos et al. 2018). Both studies did not differentiate between COO subtypes (Davids et al. 2017, de Vos et al. 2018). Further phase I/II trials of venetoclax combination therapy in DLBCL are currently being conducted or planned.

Cases in which immune evasion occurs through expression of PD1 ligands may benefit from PD:PD-L immune checkpoint inhibitors (Pasqualucci et al. 2018). CD19 CAR-T cells also represent a therapeutic option and target both subtypes. Initial clinical trials showed partial or complete responses in 82% (63 of 77 DLBCL patients) (Neelapu et al. 2017) and 50% (7 of 14 patients, 6 of 7 patients thereby with complete response), respectively (Schuster et al. 2017).

In addition to its immunomodulatory properties, the drug lenalidomide indirectly causes a reduced expression of IRF4, a central factor of the NF-kB signalling pathway (Lu et al. 2014, Kronke et al. 2014). 19% (Wiernik et al. 2008) and 28% (Witzig et al. 2011) of patients with refractory or relapsed DLBCL responded to monotherapy. Interestingly, depending on the therapeutic context, different patient subgroups benefit. When lenalidomide was combined with the R-CHOP regimen in newly diagnosed DLBCL in a phase II trial, this mitigated the negative prognostic impact of the non-GCB subtype (Nowakowski et al. 2015). In contrast, a phase III trial of the use of lenalidomide as maintenance therapy after R-CHOP treatment showed the strongest effects compared to placebo control in patients with GCB-DLBCL (Thieblemont et al. 2017).

The dependence of the ABC subtype on a constitutively activated B-cell receptor signalling pathway opens up ABC-DLBCL specific therapeutic options. For example, the Bruton tyrosine kinase BTK is a key interface between the B-cell receptor signalling pathway and the downstream NF-kB signalling pathway. The BTK inhibitor ibrutinib, currently used to treat CLL, mantle cell lymphoma and Waldenström's disease, is being evaluated in this context. However, preliminary studies on the use of ibrutinib in DLBCL are contradictory. In ibrutinib monotherapy of refractory or relapsed DLBCL, 37% of ABC-DLBCL patients responded in a phase II trial, but only 5% of patients with GCB-DLBCL did - consistent with the underlying biological characteristics (Wilson et al. 2015). In previously untreated non-GCB-DLBCL or ABC-DLBCL, the combination of ibrutinib and R-CHOP did not confer an advantage in event-free survival over placebo control in the overall group. Only the under-65 subgroup benefited in overall, event-free and progression-free survival from R-CHOP + ibrutinib combination therapy (Younes et al. 2018). Resistance to ibrutinib through compensatory mechanisms or mutations downstream of BTK may be a reason for the conflicting observations (Herman 2018, Pon et al. 2016). Ideal therapeutic targets are factors upstream of BTK, including, for example, the tyrosine kinase Src, which is upstream of both the NF-kB and PI3K/AKT pathways (Herman 2018). Clinical trials on the use of bortezomib, a proteasome inhibitor, provided conflicting data (Dunleavy et al. 2009, Leonard et al. 2017).

Inhibitors of the PI3K and mTOR pathways are attractive therapeutic targets in GCB-DLBCL. Everolimus, an mTOR inhibitor, was evaluated in a phase II trial for refractory/relapsed DLBCL, with 38% of patients showing response (Barnes et al. 2013). In particular, cases with GCB-DLBCL may also benefit from epigenetic therapeutics (Pasqualucci et al. 2018).

Alizadeh AA et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403(6769):503-511

Barnes JA et al. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica 2013;98(4):615-619

Barrans S et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol 2010;28(20):3360-3365

Barrans SL et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res 2003;9(6):2133-2139

Barrans SL et al. Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. Br J Haematol 2002;117(2):322-332

Barth TF et al. [Round robin test for detection of genomic aberrations in non-Hodgkin lymphoma by in situ hybridization]. Pathologe 2013;34(4):329-334

Basso K et al. Germinal centres and B cell lymphomagenesis. Nat. Rev. Immunol. 2015;15(3):172-184

Basso K et al. Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells. Blood 2010;115(5):975-984

Cerchietti LC et al. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell 2010;17(4):400-411

Cerchietti LC et al. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat. Med 2009;15(12):1369-1376

Chapuy B et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 2016;127(7):869-881

Chapuy B et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat. Med 2018;24(5):679-690

Chen L et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 2008;111(4):2230-2237

Ci W et al. The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL. Blood 2009;113(22):5536-5548

Copie-Bergman C et al. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood 2015;126(22):2466-2474

Davids MS et al. Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. J Clin Oncol 2017;35(8):826-833

Davis RE et al. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp. Med 2001;194(12):1861-1874

Davis RE et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010;463(7277):88-92

de Vos S et al. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. Ann. Oncol 2018;29(9):1932-1938

Dunleavy K et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood 2009;113(24):6069-6076

Efremov DG. FOXO discriminates tonic from chronic in DLBCL. Blood 2016;127(6):669-670

Foot NJ et al. Fluorescence in situ hybridisation analysis of formalin-fixed paraffin-embedded tissue sections in the diagnostic work-up of non-Burkitt high grade B-cell non-Hodgkin's lymphoma: a single centre's experience. J Clin Pathol. 2011;64(9):802-808

Hans CP et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103(1):275-282

Herman SEM. The future of kinase inhibitors for DLBCL? Blood 2018;131(21):2278-2280

Hu S et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood 2013;121(20):4021-4031

Iqbal J et al. Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma. Leukemia 2007;21(11):2332-2343

Iqbal J et al. BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res 2011;17(24):7785-7795

Iqbal J et al. BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. J Clin. Oncol. 2006;24(6):961-968

Iqbal J et al. BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am J Pathol. 2004;165(1):159-166

Jardin F et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 2010;116(7):1092-1104

Karube K et al. Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets. Leukemia 2018;32(3):675-684

Krönke J et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 2014;343(6168):301-305

Leonard JP et al. Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol 2017;35(31):3538-3546

Lu G et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 2014;343(6168):305-309

u TX et al. MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma. Oncotarget. 2015;6(21):18374-18388

Myers DR et al. Tonic Signals: Why Do Lymphocytes Bother? Trends Immunol. 2017;38(11):844-857

Neelapu SS et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med 2017;377(26):2531-2544

Nowakowski GS et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. J Clin Oncol 2015;33(3):251-257

Pasqualucci L et al. Genetics of diffuse large B-cell lymphoma. Blood 2018;131(21):2307-2319

Pon JR et al. Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma. Blood 2016;127(2):181-186

Read JA et al. Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms. Clin Lymphoma Myeloma. Leuk. 2014;14(6):460-467

Rimsza LM et al. Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions. Blood 2006;107(3):1101-1107

Rimsza LM et al. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood 2004;103(11):4251-4258

Rosenthal A et al. High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6: Double hit and triple hit lymphomas and double expressing lymphoma. Blood Rev. 2017;31(2):37-42

Rosenwald A et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002;346(25):1937-1947

Rossi D et al. Biology and treatment of Richter syndrome. Blood 2018;131(25):2761-2772

Savage KJ et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 2009;114(17):3533-3537

Schmitz R et al. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med 2018;378(15):1396-1407

Schuster SJ et al. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med 2017;377(26):2545-2554

Scott DW et al. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. Blood 2018;131(18):2060-2064

Scott DW et al. Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies. J Clin Oncol 2015;33(26):2848-2856

Shustik J et al. Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP. Haematologica 2010;95(1):96-101

Stasik CJ et al. Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. Haematologica 2010;95(4):597-603

Swerdlow SH et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer (IARC) 2017

Swerdlow SH et al. The 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms. Blood 2016;127(20):2375-2390

Testoni M et al. Gains of MYC locus and outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP. Br J Haematol 2011;155(2):274-277

Thieblemont C et al. Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. J Clin Oncol 2017;35(22):2473-2481

Trinh DL et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood 2013;121(18):3666-3674

Tzankov A et al. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Mod. Pathol. 2014;27(7):958-971

Valentino C et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139(2):242-254

Ventura RA et al. FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. J Mol. Diagn. 2006;8(2):141-151

Visco C et al. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study. Haematologica 2013;98(2):255-263

Wiernik PH et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008;26(30):4952-4957

Wilson WH et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat. Med 2015;21(8):922-926

Witzig TE et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann. Oncol 2011;22(7):1622-1627

Wright G et al. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc. Natl. Acad. Sci. U. S. A 2003;100(17):9991-9996

Xu-Monette ZY et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2012;120(19):3986-3996

Yoon SO et al. MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type. Histopathology 2008;53(2):205-217

Younes A et al. A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2018;132(Suppl. 1):784.

Young KH et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood 2008;112(8):3088-3098

You may also be interested in


As a rapidly growing, innovative medical laboratory, we are always looking for bright minds to help us bring new and more effective therapies to patients around the world.

Learn more


Do you have questions about sample submission, analyses performed or findings? Here you will find contact details, contact persons and our most frequently asked questions (FAQs).

Learn more

Quality management

We have been certified according to national and international standards since 2009 and have successfully maintained these accreditations.

Learn more

de / en

Top Articles
Latest Posts
Article information

Author: Rob Wisoky

Last Updated: 23/05/2023

Views: 6128

Rating: 4.8 / 5 (68 voted)

Reviews: 83% of readers found this page helpful

Author information

Name: Rob Wisoky

Birthday: 1994-09-30

Address: 5789 Michel Vista, West Domenic, OR 80464-9452

Phone: +97313824072371

Job: Education Orchestrator

Hobby: Lockpicking, Crocheting, Baton twirling, Video gaming, Jogging, Whittling, Model building

Introduction: My name is Rob Wisoky, I am a smiling, helpful, encouraging, zealous, energetic, faithful, fantastic person who loves writing and wants to share my knowledge and understanding with you.