The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review

Xu, Pengpeng; Shen, Rong; Shi, Zi-Yang; Cheng, Shu; Wang, Li; Liu, Yang; Zhang, Lu; Huang, Ruiqi; Ma, Xiaopeng; Wu, Xiaolian; Yao, Hui; Yu, Yanhao; Zhao, Wei‐Li

doi:10.1016/j.clml.2022.08.006

Cited by 4 publications

(6 citation statements)

References 37 publications

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“…In mucosa-associated lymphoid (MALT) lymphoma, the chronic activation of the CD79B/BTK pathway enhances the proliferation of lymphoma cells ( 30 ). In diffuse large B-cell lymphoma, it increases cell proliferation, survival, and invasion capabilities and is widely mutated ( 30 , 31 ). Polatuzumab ( 32 , 33 ), an antibody drug conjugates(ADC) antibody drug targeting CD79B, binds to the CD20 antigen, inhibiting B cell growth and proliferation in the CD79B region, and has been proven to have therapeutic effects in specific types of lymphomas, such as DLBCL and EMZL refractory or relapsed cases.…”

Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma

Zhang

Qu²,

et al. 2023

Front. Immunol.

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BackgroundCuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients.MethodsRNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB).ResultsWe have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.

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Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma

Zhang

Qu²,

et al. 2023

Front. Immunol.

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“…This study showed potential in the tailoring of the combined targeted treatment based on the results of the mutational status in the signaling pathways in the tumor cells. Previous studies showed that CD79B mutation carries a higher risk for unfavorable outcome in patients with DLBCL ( 86 ). The preliminary results of a phase 2 study in 137 patients with CD79A / CD79B -mutant TN and R/R DLBCL found the addition of zanubrutinib to augment R-CHOP or salvage therapy ( 87 ).…”

Section: Zanubrutinib In Other Lymphoid Malignanciesmentioning

confidence: 98%

“…Perhaps these agents, including zanubrutinib, could be administered concurrently as immune modifiers after CAR-T infusion, as well as synergizing with the anti-lymphoma effect. There is a single case report on zanubrutinib combined with an oral histone deacetylase inhibitor (HDACi), chidamide, in a 70-year old patient with DLBCL who relapsed 12 months after CAR-T therapy (85). He failed salvage chemotherapy with gemcitabine, dexamethasone and cisplatin, and suffered from progressive and symptomatic lung infiltration.…”

Section: Diffuse Large B-cell Lymphomamentioning

confidence: 99%

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions

Wolska-Washer

Robak

2023

Front. Oncol.

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Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a next-generation irreversible inhibitor of Bruton’s tyrosine kinase (BTK), developed by BeiGene in 2012 for the treatment of B-cell malignancies. It was designed to minimize off-target inhibition of TEC- and EGFR-family kinases. Zanubrutinib is more selective than ibrutinib for BTK versus EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC. In addition, compared to ibrutinib, zanubrutinib has improved oral absorption and better target occupancy. Zanubrutinib demonstrated a lower incidence of off-target toxicities and reduced severity than ibrutinib. Moreover, zanubrutinib is similar to acalabrutinib, with less activity against TEC and ITK. The preliminary phase 1 results suggest that zanubrutinib has clinical activity and the drug is well tolerated in patients with B-cell lymphoid malignancies. Recent clinical trials have found it to demonstrate excellent efficacy and good tolerability in patients with chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM) and mantle cell lymphoma (MCL). In recent phase 3 studies, zanubrutinib was compared with ibrutinib in patients with relapsed/refractory (R/R) MW and RR CLL. In both trials, zanubrutinib was found to demonstrate clinically meaningful advantages in safety and tolerability over ibrutinib; in particular, it was associated with a lower risk of atrial fibrillation/flutter and major bleeding events. In the recent SEQUOIA study, comparing zanubrutinib with bendamustine and rituximab (BR) in patients with previously untreated CLL, zanubrutinib significantly improved progression-free survival versus BR, with an acceptable safety profile consistent with previous studies. Zanubrutinib also demonstrated good activity and tolerability in patients with R/R MCL, marginal zone lymphoma and follicular lymphoma. Trials examining the efficacy and safety of the combination of zanubrutinib with obinutuzumab venetoclax and other drugs are ongoing. This review summarizes the clinical efficacy and safety of zanubrutinib in lymphoid malignancies.

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“…In lymphomas, CD79B mutations also commonly co-occur with MYD88 mutations, especially MYD88 L265P . MYD88 mutations have higher prevalence in cases with extranodal localization and mediate active BCR signaling phenotype within the MCD genotype of DLBCL [ 3 , 56 , 58 , 126 , 127 , 130 , 163 , 164 , 165 ]. Multiple studies reported a combined biological effect of CD79B and MYD88 mutations.…”

Section: Cd79a and Cd79b Are Important Regulators Of Proximal And Dis...mentioning

confidence: 99%

“…Particularly, concomitant CD79B and MYD88 mutations (characteristic for the MCD class of DLBCL) are associated with worse prognosis [ 3 , 55 , 57 , 126 , 172 , 173 ]. Importantly, a recent DLBCL meta-analysis showed that CD79B mutations had higher predictive value for disease progression and treatment outcomes than MYD88 mutations [ 164 ]. Inferior survival of patients with CD79B mutations might be related to a specific disease biology and associated with an increased risk of chemo-refractory disease and relapse [ 54 ].…”

Section: Open Questions and Future Directionsmentioning

confidence: 99%

B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells

Tkachenko,

Kupcova,

Havranek

2023

IJMS

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B-cell receptor (BCR) is a B cell hallmark surface complex regulating multiple cellular processes in normal as well as malignant B cells. Igα (CD79a)/Igβ (CD79b) are essential components of BCR that are indispensable for its functionality, signal initiation, and signal transduction. CD79a/CD79b-mediated BCR signaling is required for the survival of normal as well as malignant B cells via a wide signaling network. Recent studies identified the great complexity of this signaling network and revealed the emerging role of CD79a/CD79b in signal integration. In this review, we have focused on functional features of CD79a/CD79b, summarized signaling consequences of CD79a/CD79b post-translational modifications, and highlighted specifics of CD79a/CD79b interactions within BCR and related signaling cascades. We have reviewed the complex role of CD79a/CD79b in multiple aspects of normal B cell biology and how is the normal BCR signaling affected by lymphoid neoplasms associated CD79A/CD79B mutations. We have also summarized important unresolved questions and highlighted issues that remain to be explored for better understanding of CD79a/CD79b-mediated signal transduction and the eventual identification of additional therapeutically targetable BCR signaling vulnerabilities.

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The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review

Cited by 4 publications

References 37 publications

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions

B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells

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