scholarly journals Population-Wide Introduction of Dose-Adjusted EPOCH-R Is Associated with Improved Outcome of High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements with Diffuse Large B-Cell Lymphoma Morphology

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1458-1458
Author(s):  
Waleed Alduaij ◽  
Laurie H. Sehn ◽  
Aixiang Jiang ◽  
Susana Ben-Neriah ◽  
Brett Collinge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade

Abstract Introduction: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH), colloquially referred to as double- or triple-hit lymphoma, is associated with poor outcomes prompting many centers to use dose-intensive immunochemotherapy. The benefit of treatment intensification in patients with HGBL-DH/TH with diffuse large B-cell lymphoma (DLBCL) morphology, who would otherwise receive standard-of-care rituximab, cyclophosphamide, vincristine and prednisone (R-CHOP), remains unclear because suitably powered randomized clinical trials have not been performed, and earlier studies included patients with high-grade morphology. Furthermore, selection bias due to the restriction of fluorescence in situ hybridization (FISH) testing to diagnose HGBL-DH/TH in patients with high-risk clinical presentation or aggressive tumor morphology confounds historical comparators. Since 2015, de novo DLBCL biopsies in British Columbia (BC) have undergone routine FISH testing in clinical practice. Concurrently, provincial guidelines were introduced recommending treatment with dose-adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone and rituximab (DA-EPOCH-R) for appropriately fit patients aged 75 years (y) or younger with HGBL-DH/TH harboring BCL2 rearrangements with DLBCL morphology (HGBL-DH/TH-BCL2-DLBCL). A population-based analysis was conducted to assess the impact of the introduction of DA-EPOCH-R on outcomes in HGBL-DH/TH-BCL2-DLBCL. Methods: Outcomes of HGBL-DH/TH-BCL2-DLBCL patients diagnosed between 2015 to 2020 using clinical FISH performed on de novo DLBCL biopsies (DA-EPOCH-R era) were compared to patients with HGBL-DH/TH-BCL2-DLBCL identified from a historic province-wide cohort of de novo DLBCL diagnosed between 2005-2010 in BC that underwent universal FISH in a research setting (R-CHOP era). Patients with the rarer entity of HGBL-DH/TH harboring MYC and BCL6 rearrangements only (HGBL-DH-BCL6) were excluded and were not part of the original DA-EPOCH-R guideline. Multivariable Cox proportional hazards regression models were used to predict the independent effect of treatment era after controlling for the International Prognostic Index (IPI). Results: 99 patients with HGBL-DH/TH-BCL2-DLBCL were identified through routine clinical FISH in the DA-EPOCH-R era. Of 1172 de novo DLBCL patients in the historic R-CHOP era, 824 had adequate diagnostic material for evaluation by FISH, 52 of which were HGBL-DH/TH-BCL2-DLBCL. The analysis was restricted to patients aged 75y or younger, yielding 71 and 38 patients in the DA-EPOCH-R and R-CHOP eras, respectively. 7/38 (18%) biopsies in the R-CHOP era had undergone clinical FISH testing at diagnosis with results known to the treating physician. Median (interquartile range) follow-up in living patients was 2.8y (2.0-4.4y) in the DA-EPOCH-R era and 12.2y (11.2-13.4y) in the R-CHOP era. 49/71 (69%) patients received DA-EPOCH-R in the DA-EPOCH-R era, whereas 32/38 patients (84%) received R-CHOP in the R-CHOP era. Both eras had comparable baseline clinical characteristics with no significant difference in IPI risk groups (Table 1). The DA-EPOCH-R era was associated with superior 2-year time to progression (TTP, 73.9% vs 47.4%, p=0.016) and overall survival (OS, 77.7% vs 50.0%, p=0.022, Figure 1). After adjusting for IPI risk groups (low 0-2, high 3-5), the DA-EPOCH-R era was independently associated with superior TTP (hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.21-0.77, p=0.005) and OS (HR 0.39, 95% CI 0.21-0.76, p=0.005). After controlling for individual IPI factors, treatment era remained predictive of TTP (HR 0.38, 95% CI 0.19- 0.76, p=0.006) and OS (HR 0.39, 95% CI 0.19-0.79, p=0.008). Conclusions: Introduction of a provincial, population-based recommendation to use DA-EPOCH-R for appropriately fit patients aged 75y or younger is associated with improved real-world outcomes of HGBL-DH/TH-BCL2-DLBCL. The similarity between TTP and OS within each era suggests the high failure rate of conventional salvage therapy irrespective of frontline treatment, prompting further investigation of novel second-line therapies in this poor-prognosis population. Targeted capture sequencing to identify MYC translocation partners is underway, and the influence of the MYC partner on outcomes in both eras will be presented. Figure 1 Figure 1. Disclosures Sehn: Novartis: Consultancy; Genmab: Consultancy; Debiopharm: Consultancy. Slack: Seagen: Consultancy, Honoraria. Craig: Bayer: Consultancy. Villa: Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria; NanoString Technologies: Honoraria. Gerrie: Sandoz: Honoraria; Roche: Research Funding; Astrazeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Freeman: Teva: Research Funding; Roche: Research Funding; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Incyte: Honoraria; Abbvie: Honoraria; Seattle Genetics: Honoraria; Bristol Myers Squibb: Honoraria, Speakers Bureau. Savage: Seattle Genetics: Consultancy, Honoraria; Roche: Research Funding; Astra-Zeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Servier: Consultancy, Honoraria; Takeda: Other: Institutional clinical trial funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Steidl: Bayer: Consultancy; Trillium Therapeutics: Research Funding; Curis Inc.: Consultancy; AbbVie: Consultancy; Epizyme: Research Funding; Seattle Genetics: Consultancy; Bristol-Myers Squibb: Research Funding. Scott: Celgene: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Rich/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Incyte: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy.

Immunohistochemical Classification of De Novo, Transformed, and Relapsed Diffuse Large B-Cell Lymphoma Into Germinal Center B-Cell and Nongerminal Center B-Cell Subtypes Correlates With Gene Expression Profile and Patient Survival

2006 ◽  
Vol 130 (12) ◽  
pp. 1819-1824 ◽  
Author(s):  
Chadwick F. Haarer ◽  
Robin A. Roberts ◽  
Yvette M. Frutiger ◽  
Thomas M. Grogan ◽  
Lisa M. Rimsza
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
De Novo ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell

Abstract Context.—Diffuse large B-cell lymphoma (DLBCL) can be assigned to prognostic subgroups, including germinal center B-cell (GCB) and activated B-cell subgroups, by using gene expression profiling and, reportedly, immunohistochemistry for CD10, Bcl-6, and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4). Objective.—To compare 2 commercial MUM1/IRF4 antibody formulations for accuracy in subtyping DLBCL against gene expression profiling, compare subtyping to patient survival, and evaluate the usefulness of GCB and non-GCB subtyping in relapsed and transformed DLBCL. Design.—Evaluation of 2 commercial MUM1/IRF4 antibodies, ICSTAT/M17 and Mum-1p, by using 40 cases of de novo, relapsed, and transformed DLBCL; and comparison of the results obtained with gene expression profiling and survival. Results.—Immunohistochemistry predicted the gene expression profiling subtype 71.8% and 69.2% of the time overall with use of the Mum-1p and ICSTAT/M17 antibodies, respectively, and 100% and 91.7% of the time when MUM1/IRF4 expression determined subtype. Gene expression profiling and immunohistochemistry revealed nearly identical 5-year overall survival rates for the GCB vs non-GCB subtypes (68.0% for GCB vs 24.7% for non-GCB with use of gene expression profiling [P = .03] and 70.2% vs 18.4%, respectively, with use of immunohistochemistry [P < .001]). When de novo, transformed, and relapsed cases were analyzed separately, 5-year overall survival rates were also significantly different. Conclusions.—Immunohistochemistry can be used to subclassify DLBCL, including a very small series of transformed and relapsed cases, into GCB and non-GCB subtypes and predict survival rates similar to those predicted by use of gene expression profiling. The 2 MUM1/IRF4 antibodies performed similarly.

Loss of Major Histocompatibility Class II (MHCII) Gene Expression in Diffuse Large B Cell Lymphoma (DLBCL) Is Not Generally Due to Genetic Mutations in the Coding Regions of CIITA or RFX.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2039-2039 ◽  
Author(s):  
Robin A. Roberts ◽  
Thomas P. Miller ◽  
Lisa M. Rimsza
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Mutations ◽  
Coding Region ◽  
Mhcii Expression

Abstract Loss of expression of the MHCII in a subset of DLBCL cases studied by the Leukemia and Lymphoma Molecular Profiling Project (LLMPP) has been previously associated with extremely poor prognosis. Large genetic deletions of the MHC II loci were not seen in these cases. Furthermore, gene expression profiling analysis demonstrated that the MHCII gene expression was coordinated and most likely suppressed through altered transcription. We therefore investigated the possibility of small deletions or genetic mutations of 2 key transcriptional regulators of MHCII, CIITA and RFX, as possible causes of decreased MHCII expression in DLBCL. These transcription factors were chosen because mutations in the coding region of these proteins have been shown to cause the rare genetic disease, bare lymphocyte syndrome, in which MHCII expression is lost. We designed primers to amplify all coding exons of CIITA and RFX (a multimer containing RFX5, RFXB, and RFXAP), including internal splicing regions, in a minimal number of amplifications. DNA samples were amplified by 6 multiplex PCRs of genomic DNA, then the products sequenced with separate sequencing primers and compared to NCBI curated sequences. DLBCL DNA samples for which gene expression profiling data on MHCII expression was available, were obtained from the LLMPP research group. 23 of these samples were from the lowest 10% de novo untreated average MHCII expressers, 4 from non-de novo samples expressing MHCII in the same range, 4 from low MHCII expressers in the lowest 10–25% range, and 15 were primary mediastinal B cell lymphoma (PMBL) samples. The PMBL subset of DLBCL expresses MHCII at a lower range than other DLBCL. A number of other MHCII positive and negative lymphoma samples and cell lines were also sequenced. Although various SNPs and silent changes were noted, there were few small point mutations, deletions, or splicing mutations in the low MHCII DLBCL expressers that would explain loss of MHCII expression. In RJ2.2.5, an MHCII negative Burkitts lymphoma cell line derived from Raji, which is known to have only one CIITA allele expressing RNA lacking exons 11 and 12, the genomic deletion was sequenced. One of the lowest 10% MHCII expressing LLMPP samples had an insertional duplication that caused a frameshift in the C-terminus of all copies of the CIITA gene. Another tumor sample showing functional mutations was an MHCII negative T cell lymphoma (non-LLMPP), which had nonsense mutations in both RFXAP and RFX5, all copies. In conclusion, critical deletions or mutations were not common in the studied samples. These results confirmed previous data implying loss of MHCII expression in DLBCL was most likely due to altered transcriptional regulation, and indicate that this unfortunate circumstance may frequently be amenable to therapeutic intervention to upregulate the MHCII pathway.

A Prospective Randomised Trial of Targeted Therapy for Diffuse Large B-Cell Lymphoma (DLBCL) Based upon Real-Time Gene Expression Profiling: The Remodl-B Study of the UK NCRI and SAKK Lymphoma Groups (ISRCTN51837425)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 812-812 ◽  
Author(s):  
Andrew J Davies ◽  
Josh Caddy ◽  
Tom Maishman ◽  
Sharon Barrans ◽  
Christoph Mamot ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
Adaptive Design ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: DLBCL subtypes may be classified by gene expression corresponding to germinal centre (GCB) or activated peripheral blood (ABC) B-cells. Treatment outcomes with R-CHOP therapy were inferior for ABCs in retrospective series, and this study investigated whether adding bortezomib could reverse the adverse prognosis. The trial used gene expression profiling (GEP) to stratify cases, with adaptive design to analyse the outcome by subtypes at predefined timepoints. Methods: Newly diagnosed patients with DLBCL underwent staging and commenced standard R-CHOP. During cycle 1, formalin-fixed paraffin-embedded (FFPE) tissue was used to extract messenger RNA for GEP using the Illumina DASL array platform. Cases were allocated to GCB, ABC or Unclassifiable (Unc) type before starting cycle 2, using an established algorithm based upon 20 genes. Patients with successful GEP were randomised 1:1 to receive R-CHOP +/- bortezomib 1.6 mg/m2 s/c on days 1+8 in cycles 2-6. The study was powered to detect a difference in progression-free survival (PFS) of 10% with bortezomib, with a 2-sided significance, 5% and 90% power. The adaptive design allowed for closure of randomization for GCB cases if 1-year PFS was <70% after 55 received RB-CHOP (interim safety analysis) or if 1-year PFS was <85% after 73 received RB-CHOP and followed for 1 year (futility analysis). Results: Between 6/2011 and 5/2015 1132 patients were enrolled from 109 sites, with 1078 samples analysed. Of these, 157 (15%) biopsies had inadequate material for GEP, but the remaining 921 were classified as 246 (27%) ABC, 476 (52%) GCB and 199 (22%) Unc. Successful classification was possible from both surgical and needle core biopsies. Median laboratory turnaround time was 12 working days and all results were available prior to the scheduled administration of cycle 2. Characteristics of the patients of different subtypes are shown in the table. Following both interim analyses the DMEC recommended continued recruitment of patients with a GCB phenotype. Table. ABC GCB Unc Age (years): median 67 63 63 Age (years) : range 23 to 86 20 to 82 20 to 85 % performance status 0-1 88 88 90 % at least one extranodal site 53 54 62 % bone marrow involved 15 14 23 % LDH>ULN 69 76 79 % IPI score 0/1 29 27 26 % IPI score 2/3 57 55 55 % IPI score 4/5 15 19 19 % B symptoms 46 43 49 % Bulk>10cm 17 26 21 Conclusions: This study has demonstrated the feasibility of GEP at diagnosis to subsequently guide therapy in a large multicentre trial. Although patients with ABC type lymphoma were in general slightly older, they did not appear to have other adverse prognostic features at diagnosis vs GCB. All patients will have completed therapy by the time of the meeting, allowing the initial response and toxicity data to be available for presentation. Disclosures Davies: GIlead: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; CTI: Honoraria; Takeda: Honoraria, Research Funding; Bayer: Research Funding; GSK: Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Pfizer: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: The addition of bortezomib to R-CHOP chemotherapy in diffuse large B-cell lymphoma. Pocock:Janssen: Honoraria. Jack:Jannsen: Research Funding. Johnson:Takeda: Honoraria; Pfizer: Honoraria; Janssen: Research Funding.

Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the Clinic?

2015 ◽  
pp. e458-e466 ◽  
Author(s):  
David W. Scott
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Practical Implementation ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide and consists of a heterogeneous group of cancers classified together on the basis of shared morphology, immunophenotype, and aggressive clinical behavior. It is now recognized that this malignancy comprises at least two distinct molecular subtypes identified by gene expression profiling: the activated B-cell-like (ABC) and the germinal center B-cell-like (GCB) groups—the cell-of-origin (COO) classification. These two groups have different genetic mutation landscapes, pathobiology, and outcomes following treatment. Evidence is accumulating that novel agents have selective activity in one or the other COO group, making COO a predictive biomarker. Thus, there is now a pressing need for accurate and robust methods to assign COO, to support clinical trials, and ultimately guide treatment decisions for patients. The “gold standard” methods for COO are based on gene expression profiling (GEP) of RNA from fresh frozen tissue using microarray technology, which is an impractical solution when formalin-fixed paraffin-embedded tissue (FFPET) biopsies are the standard diagnostic material. This review outlines the history of the COO classification before examining the practical implementation of COO assays applicable to FFPET biopsies. The immunohistochemistry (IHC)-based algorithms and gene expression–based assays suitable for the highly degraded RNA from FFPET are discussed. Finally, the technical and practical challenges that still need to be addressed are outlined before robust gene expression–based assays are used in the routine management of patients with DLBCL.

scholarly journals Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells

2001 ◽  
Vol 194 (12) ◽  
pp. 1861-1874 ◽  
Author(s):  
R. Eric Davis ◽  
Keith D. Brown ◽  
Ulrich Siebenlist ◽  
Louis M. Staudt
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Nuclear Factor ◽  
Large B Cell Lymphoma ◽  
Dlbcl Subtype ◽  
Large B Cell

Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell–like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-κB transcription factors, raising the possibility that constitutive activity of the NF-κB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-κB DNA binding activity, constitutive IκB kinase (IKK) activity, and rapid IκBα degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form of IκBα or dominant negative forms of IKKβ was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-κB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-κB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms.

Gene Expression Profiling of Diffuse Large B-Cell Lymphomas Supervised by CD5 Expression

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4164-4164
Author(s):  
Kana Miyazaki ◽  
Motoko Yamaguchi ◽  
Hiroshi Imai ◽  
Satoshi Tamaru ◽  
Tohru Kobayashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Set ◽  
Large B Cell Lymphoma ◽  
The Difference ◽  
Large B Cell

Abstract Abstract 4164 Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is composed of heterogeneous groups of lymphoma with pathophysiological, genetic and clinical features. Gene expression profiling identified two distinct forms of DLBCL: activated B cell-like (ABC) and germinal center B-cell-like (GCB) types. ABC DLBCL shows more activated phenotype characterized with high activity of the NF-kappa B pathway and worse prognosis than GCB DLBCL. CD5-positive (CD5+) DLBCL comprises 5 to 10% of DLBCL and is one of the immunohistochemical subgroups in the 2008 WHO classification. It shows many distinct clinical characteristics with elderly onset, advanced stage at diagnosis, high serum lactate dehydrogenase level and frequent involvement of extranodal sites. Despite the use of rituximab, CD5+ DLBCL shows a poor prognosis and high incidence of central nervous system (CNS) relapse. More than 80% of patients with CD5+ DLBCL are classified as non-GCB subgroup by Hans' method; however, few molecular studies have been reported. To clarify the difference between CD5+ DLBCL and CD5-negative (CD5-) DLBCL in the gene expression profile, total RNA from 90 patients with de novo DLBCL including 33 CD5+ DLBCLs and 57 CD5- DLBCLs was examined using Agilent 44K human oligo-microarrays (Agilent 4112F). The expression of CD5 in tumor cells was confirmed by means of immunohistochemistry using frozen sections. Cases of primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma and primary DLBCL of the CNS were excluded from the present study. Supervised hierarchical clustering of the expression data could separate the DLBCL cases into the two groups, CD5+ DLBCL and CD5- DLBCL. A signature gene set supervised by CD5 expression included some of the same genes (SH3BP5, CCND2, LMO2) in the predictor gene set to discriminate between GCB and ABC DLBCLs. To classify the difference between CD5+ ABC DLBCL and CD5- ABC DLBCL in the gene expression profile, the 90 DLBCLs were analyzed by the Rosenwald's gene set (NEJM, 2002). Those cases were separated with 78 ABC DLBCLs and 12 GCB DLBCLs. Incidence of CD5+ cases was 42% (33/78) in ABC DLBCLs and 0% in GCB DLBCLs. A classifier based on gene expression at supervised analysis also correctly identified CD5 expression in ABC DLBCL. Signature genes to distinguish between CD5+ ABC DLBCL and CD5- ABC DLBCL were as follows: SNAP25, SYCP3, CCNA1, MAPK4, CCNA1, LMO3, NLGN3, GRIN2A, AQP4, FGFR2, NEUROD1, KL, FGF1, SYT5, etc., were overexpressed in CD5+ ABC DLBCL, and CYP4Z1, MDM2, IL7R, GRLF1, TNFRSF9, CD1A etc., were overexpressed in CD5- ABC DLBCL. Enriched Gene Ontology (GO) categories in CD5+ ABC DLBCL were synapse, multicellular organismal process, fibroblast growth factor receptor signaling pathway, cell projection, alcohol dehydrogenase activity and glucuronosyltransferase activity. Among them, synapse was the top GO category (P=6.1E-05). In conclusion, our current study confirmed that most of CD5+ DLBCLs are classified as ABC DLBCL by gene expression profiling. Our results suggest that neurological component- and function-related genes in the CD5+ ABC DLBCL signature gene set may be related to the high frequency of CNS relapse in CD5+ DLBCL. Disclosures: No relevant conflicts of interest to declare.

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