Coexpression of <scp>CD</scp>5 and <scp>CD</scp>43 predicts worse prognosis in diffuse large B‐cell lymphoma

Ma, Xiaobo; Zhong, Yi; Zheng, Yan; Jiang, Jing; Wang, Yin‐ping

doi:10.1002/cam4.1674

“…Chien et al examined CLA expression in almost 90 AML patient samples from the peripheral blood and the BM and found a 4-fold higher expression for relapsed/refractory patients than for newly diagnosed AML patients [ 17 ]. These results were in line with increased CLA expression in cancerous plasma cells from relapsed/refractory patients compared to newly diagnosed MM patients [ 15 , 47 , 48 ]. Moreover, it was shown that CLA was increased in hypoxic MM cells, indicating the progression of MM to more advanced stages.…”

Section: The Role Of E-selectin In Cancer Pathophysiologysupporting

confidence: 69%

Targeting E-selectin to Tackle Cancer Using Uproleselan

Muz

¹

,

Abdelghafer

²

,

Markovic

³

et al. 2021

Cancers

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E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer. Uproleselan (also known as GMI-1271), a specific E-selectin antagonist, has been tested on leukemia, myeloma, pancreatic, colon and breast cancer cells, most of which involve the bone marrow as a primary or as a metastatic tumor site. This novel therapy disrupts the tumor microenvironment by affecting the two main steps of metastasis—extravasation and adhesion—thus blocking E-selectin reduces tumor dissemination. Additionally, uproleselan mobilized cancer cells from the protective vascular niche into the circulation, making them more susceptible to chemotherapy. Several preclinical and clinical studies summarized herein demonstrate that uproleselan has favorable safety and pharmacokinetics and is a tumor microenvironment-disrupting agent that improves the efficacy of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E-selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.

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“…Moreover, some promising targets have been detected for the prevention and treatment of relapsed/refractory DLBCL [ 8 ]. For instance, coexpression of CD5 and CD43 may predict a poor prognosis of DLBCL patients [ 9 ]. A high NEAT1_1 level is positively correlated with stage, IPI, extranodal involvement, drug response, and poor prognosis [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Distinct Molecular Subtypes of Diffuse Large B Cell Lymphoma Patients Treated with Rituximab‐CHOP Are Associated with Different Clinical Outcomes and Molecular Mechanisms

Yu

¹

,

Peng

²

,

Han

³

et al. 2021

BioMed Research International

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Objective. Our purpose was to characterize distinct molecular subtypes of diffuse large B cell lymphoma (DLBCL) patients treated with rituximab-CHOP (R-CHOP). Methods. Two gene expression datasets of R-CHOP-treated DLBCL patients were downloaded from GSE10846 ( n = 233 , training set) and GSE31312 ( n = 470 , validation set) datasets. Cluster analysis was presented via the ConsensusClusterPlus package in R. Using the limma package, differential expression analysis was utilized to identify feature genes. Kaplan-Meier survival analysis was presented to compare the differences in the prognosis between distinct molecular subtypes. Correlation between molecular subtypes and clinical features was analyzed. Based on the sets of highly expressed genes, biological functions were explored by gene set enrichment analysis (GSEA). Several feature genes were validated in the molecular subtypes via qRT-PCR and western blot. Results. DLBCL samples were clustered into two molecular subtypes. Samples in subtype I displayed poorer overall survival time in the training set ( p < 0.0001 ). Consistently, patients in subtype I had shorter overall survival ( p = 0.0041 ) and progression-free survival time ( p < 0.0001 ) than those in subtype II. Older age, higher stage, and higher international prognostic index (IPI) were found in subtype I. In subtype I, T cell activation, lymphocyte activation, and immune response were distinctly enriched, while cell adhesion, migration, and motility were significantly enriched in subtype II. T cell exhaustion-related genes including TIM3 ( p < 0.001 ), PD-L1 ( p < 0.0001 ), LAG3 ( p < 0.0001 ), CD160 ( p < 0.001 ), and CD244 ( p < 0.001 ) were significantly highly expressed in subtype I than subtype II. Conclusion. Two molecular subtypes were constructed in DLBCL, which were characterized by different clinical outcomes and molecular mechanisms. Our findings may offer a novel insight into risk stratification and prognosis prediction for DLBCL patients.

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“…B-1 cells are somewhat resistant to rituximab, and this has implications for treatment outcome because B-1 cells have immune regulatory properties. 28,29 The resistance to B-1 cells to rituximab has also been seen in mice. 30 These B-1 cells are almost always negative for CD24 and thus distinct from the memory B cells.…”

Section: Discussionmentioning

confidence: 98%

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy

Stanwyck

¹

,

Chan

²

,

Sood

³

et al. 2020

Trans. Vis. Sci. Tech.

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To determine if immunological markers (1) are significantly different between autoimmune retinopathy (AIR) patients and controls and (2) correlate with disease progression in AIR patients. Methods: We enrolled patients with a possible AIR diagnosis, as well as control participants without eye disease, autoimmunity, or cancer. Immunological markers were tested in all participants. In addition, AIR patients had up to three blood draws for testing over their disease course. For AIR patients, clinical measures, including visual acuity (VA) and Goldmann visual field (GVF) area, were recorded at each draw. We used the Mann-Whitney U test to compare the immunological markers between AIR patients and controls. We used multilevel mixed-effect regression to investigate the correlation between markers and clinical parameters over time in AIR patients. Results: Seventeen patients with AIR and 14 controls were included. AIR patients had a higher percent of monocytes (Z = 3.076, P = 0.002). An increase in immunoglobulin G against recoverin was correlated with a VA decrease (β = 0.0044, P < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (β = −7.27, P = 0.0021). Several markers of B-cell depletion were correlated with GVF improvement. Conclusions: Monocytes may play a role in AIR pathophysiology and be a disease activity marker. B-cell depletion markers correlated with clinical parameter improvement, particularly GVF. Translational Relevance: This work elucidates immunologic markers that may improve the accuracy of diagnosis and treatment of AIR.

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Coexpression of CD5 and CD43 predicts worse prognosis in diffuse large B‐cell lymphoma

Cited by 13 publications

References 58 publications

Targeting E-selectin to Tackle Cancer Using Uproleselan

Targeting E-selectin to Tackle Cancer Using Uproleselan

[Retracted] Distinct Molecular Subtypes of Diffuse Large B Cell Lymphoma Patients Treated with Rituximab‐CHOP Are Associated with Different Clinical Outcomes and Molecular Mechanisms

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy

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