Large B Cell Lymphoma
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2022 ◽  
Vol 70 (2) ◽  
pp. 103331
David Beauvais ◽  
Adeline Cozzani ◽  
Anne-Sophie Blaise ◽  
Anne-Sophie Moreau ◽  
Pauline Varlet ◽  

ESMO Open ◽  
2022 ◽  
Vol 7 (1) ◽  
pp. 100363
S.F. Lee ◽  
B.A. Vellayappan ◽  
L.C. Wong ◽  
C.L. Chiang ◽  
S.K. Chan ◽  

eJHaem ◽  
2022 ◽  
Vincent Ribrag ◽  
Julio C. Chavez ◽  
Carola Boccomini ◽  
Jason Kaplan ◽  
Jason C. Chandler ◽  

2022 ◽  
Anne M. R. Schrader ◽  
Ruben A. L. de Groen ◽  
Rein Willemze ◽  
Patty M. Jansen ◽  
Koen D. Quint ◽  

Abstract Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

2022 ◽  
Vol 10 (2) ◽  
pp. 709-716
Zhi-Nan Fan ◽  
Hong-Jin Shi ◽  
Bo-Bo Xiong ◽  
Jin-Song Zhang ◽  
Hai-Feng Wang ◽  

Richard T Maziarz ◽  
Jie Zhang ◽  
Hongbo Yang ◽  
Xinglei Chai ◽  
Chengbo Yuan ◽  

No head-to-head trials have compared the efficacy of tisagenlecleucel versus historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (NCT02445248), versus historical treatments assessed in the CORAL study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intent-to-treat [ITT]) study populations, the JULIET FAS vs. the CORAL follow-up FAS and JULIET ITT vs. CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% CI], both FSW and SMRW: 0.44 [0.32, 0.59]) and ITT populations (FSW: 0.60 [0.44, 0.77], SMRW: 0.57 [0.44, 0.73]; all p<0.001). Median OS was 12.48 months (JULIET) vs. 4.34-4.40 months (CORAL) for the FAS, and 8.25 (JULIET) vs. 4.04-4.86 (CORAL) for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared to historical treatments among the FAS (adjusted response rate difference [95% CI], both FSW and SMRW: 36% [22%, 0.48%]; p<0.001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; p=0.043). This analysis supports that improved response and OS are achieved in r/r DLBCL patients treated with tisagenlecleucel when compared to those treated with alternative historical treatments.

2022 ◽  
Vol 8 (1) ◽  
Wei Song ◽  
Fei Fei ◽  
Fengchang Qiao ◽  
Zuyi Weng ◽  
Yuanxun Yang ◽  

AbstractLong noncoding RNAs (lncRNAs) have crucial functions in the tumorigenesis and metastasis of cancers. N6-methyladenosine (m6A) modification of RNA is an important epigenetic regulatory mechanism in various malignancies. Nevertheless, the mechanism of m6A-modified lncRNA in diffuse large B cell lymphoma (DLBCL) has remained poorly defined. In the present study, we showed that lncRNA TRERNA1 was associated with the poor prognosis of DLBCL patients. TRERNA1 with internal m6A modification was highly correlated with the demethylase ALKBH5 expression. We further demonstrated that TRERNA1 was a potential downstream target of ALKBH5-mediated m6A modification by m6A-RNA sequencing and m6A-RIP assays. Decreased m6A methylation of TRERNA1 regulated by ALKBH5 was shown to regulate cell proliferation in vitro and in vivo. The results of mechanism analyses revealed that TRERNA1 recruited EZH2 to epigenetically silence the expression of the cyclin-dependent kinases inhibitor p21 by H3K27me3 modification of its promoter region. In addition, ALKBH5 further inhibited p21 expression. Taken together, our results elucidate the functional roles and epigenetic alterations of TRERNA1 through m6A modification in DLBCL. TRERNA1, the expression of which is upregulated by ALKBH5, acts as a scaffold that decreases p21 expression. The results of the present study provide novel targets for the diagnosis and treatment of DLBCL.

Viswanatha Kartik Sambaturu ◽  
Harikrishnan K. N. Kurup ◽  
Arun Gopalakrishnan ◽  
Kavassery Mahadevan Krishnamoorthy

2022 ◽  
Vol 2022 ◽  
pp. 1-30
Cancan Luo ◽  
Han Nie ◽  
Li Yu

Diffuse large B-cell lymphoma (DLBCL) is a complex invasive tumour that occurs mainly among the elderly. Therefore, we analysed the relationship between ageing-related genes (AG) and DLBCL prognosis. Datasets related to DLBCL and human AGs were downloaded and screened from the Gene Expression Omnibus (GEO) database and HAGR website, respectively. LASSO and Cox regression were used to analyse AGs in the dataset and construct an AG predictive model related to DLBCL prognosis. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment were used to analyse the function of the AG predictive model. The immune microenvironment and immune cell infiltration in DLBCL and their relationship with the AG prediction model were also analysed. After the analysis, 118 AGs were identified as genes related to DLBCL prognosis. Using the LASSO and Cox regression analyses, 9 AGs (PLAU, IL7R, MYC, S100B, IGFBP3, NR3C1, PTK2, TBP, and CLOCK) were used to construct an AG prognostic model. In the training and verification sets, this model exhibited excellent predictive ability for the prognosis of patients with DLBCL who have different clinical characteristics. Further analysis revealed that the high- and low-risk groups of the AG prognostic model were significantly correlated with immune cell infiltration and tumour microenvironment in DLBCL. Functional enrichment analysis also showed that the genes in the AG model were associated with immune-related functions and pathways. In conclusion, we constructed an AG model with a strong predictive function in DLBCL, with the ability to predict the prognosis of patients with different clinical features. This model provides new ideas and potential therapeutic targets for the study of the pathogenesis of DLBCL.

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