scholarly journals Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

2020 ◽  
Author(s):  
Haoyu Ruan ◽  
Zhe Wang ◽  
Yue Zhai ◽  
Ying Xu ◽  
Linyu Pi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Great Promise ◽  
Leptomeningeal Involvement

AbstractDiffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

scholarly journals Analysis of Cellular Heterogeneity in Immune Microenvironment of Primary Central Nervous System Lymphoma by Single-Cell Sequencing

2021 ◽  
Vol 11 ◽  
Author(s):  
Boyuan Wei ◽  
Zhe Liu ◽  
Yue Fan ◽  
Shuwei Wang ◽  
Chao Dong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Fetal Brain ◽  
Central Nervous System Lymphoma ◽  
Cellular Heterogeneity ◽  
Significant Heterogeneity ◽  
Cellular Interactions

BackgroundPrimary central nervous system lymphoma (PCNSL) is characterized by a lack of specificity and poor prognosis. Further understanding of the tumor heterogeneity and molecular phenotype of PCNSL is of great significance for improving the diagnosis and treatment of this disease.MethodsTo explore the distinct phenotypic states of PCNSL, transcriptome-wide single-cell RNA sequencing was performed on 34,851 PCNSL cells from patients. The cell types, heterogeneity, and gene subset enrichment of PCNSL were identified. A comparison of the PCNSL cells with 21,250 normal human fetal brain (nHFB) cells was further analyzed to reveal the differences between PCNSL and normal sample.ResultsSix cell populations were mainly identified in the PCNSL tissue, including four types of immune cells—B cell, T cell, macrophage and dendritic cell—and two types of stromal cells: oligodendrocyte and meningeal cell. There are significant cellular interactions between B cells and several other cells. Three subpopulations of B cells indicating diffident functions were identified, as well as a small number of plasma cells. Different subtypes of T cells and dendritic cells also showed significant heterogeneity. It should be noted that, compared with normal, the gene expression and immune function of macrophages in PCNSL were significantly downregulated, which may be another important feature of PCNSL in addition to B cell lesions and may be a potential target for PCNSL therapy.

Targeting the PI3K/AKT/mTOR Signaling Pathway in Primary Central Nervous System Lymphoma: Current Status and Future Prospects

2020 ◽  
Vol 19 (3) ◽  
pp. 165-173
Author(s):  
Xiaowei Zhang ◽  
Yuanbo Liu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Signaling Pathway ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Antitumor Effects ◽  
Term Survival

Primary Central Nervous System Lymphoma (PCNSL) is a rare invasive extranodal non- Hodgkin lymphoma, a vast majority of which is Diffuse Large B-Cell Lymphoma (DLBCL). Although high-dose methotrexate-based immunochemotherapy achieves a high remission rate, the risk of relapse and related death remains a crucial obstruction to long-term survival. Novel agents for the treatment of lymphatic malignancies have significantly broadened the horizons of therapeutic options for PCNSL. The PI3K/AKT/mTOR signaling pathway is one of the most important pathways for Bcell malignancy growth and survival. Novel therapies that target key components of this pathway have shown antitumor effects in many B-cell malignancies, including DLBCL. This review will discuss the aberrant status of the PI3K/AKT/mTOR signaling pathways in PCNSL and the application prospects of inhibitors in hopes of providing alternative clinical therapeutic strategies and improving prognosis.

Primary Central Nervous System Lymphoma Mimicking Longitudinally Extensive Transverse Myelitis

2020 ◽  
pp. 194187442096756
Author(s):  
Prashant Anegondi Natteru ◽  
Shashank Shekhar ◽  
Lakshmi Ramachandran Nair ◽  
Hartmut Uschmann
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Oligoclonal Bands ◽  
Relative Reduction ◽  
Thalamic Lesion ◽  
The Right

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extra-nodal non-Hodgkin’s lymphoma. Three regions can be involved in PCNSL: the brain, the spine, or the vitreus and retina. Spinal PCNSL is rare. It can mimic neoplasm, infection, and inflammation. Diagnostic confirmation is by tissue biopsy, and even then, tissue corroboration may be altered by an inflammatory overlay. We report a 59-year-old woman who we saw after she had 4 weeks of ascending tetraparesis plus bowel and bladder incontinence. Upon presentation, the patient was ventilator-dependent and locked-in. She reported normal sensation through eye-blinking. Magnetic resonance imaging (MRI) brain revealed signal intensity in the bilateral corona radiata and restricted diffusion in the right thalamus, whereas, MRI cervical, and thoracic spine showed T2 prolongation in the anterior medulla and upper cervical cord, with enhancement to C2-C3, and long segment hyperintensity from T1-T9 levels, respectively, suggestive of neuromyelitis optica spectrum disorder. Cerebrospinal fluid cytomorphology and flow cytometry were inconclusive for lymphoma/leukemia, but oligoclonal bands were present. Serum aquaporin-4 (AQP-4) antibodies were negative. MR spectroscopy demonstrated NAA reduction, mild lipid lactate peak, and relative reduction of choline on the side of the lesion, favoring demyelination. She received 5-days of intravenous methylprednisolone, followed by 7 sessions of plasma exchange without clinical improvement. Stereotactic biopsy of the right thalamic lesion revealed diffuse large B-cell lymphoma. PCNSL can mimic a demyelinating process early on, as steroid treatment could disrupt B-cell lymphoma cells, thus masking the correct diagnosis.

scholarly journals T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presenting as a Primary Central Nervous System Lymphoma

Rare Tumors ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 160-162 ◽  
Author(s):  
Pooja Advani ◽  
Jason Starr ◽  
Abhisek Swaika ◽  
Liuyan Jiang ◽  
Yushi Qiu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Pathway analysis of primary central nervous system lymphoma

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3200-3210 ◽  
Author(s):  
Han W. Tun ◽  
David Personett ◽  
Karen A. Baskerville ◽  
David M. Menke ◽  
Kurt A. Jaeckle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Pathway Analysis ◽  
Metastatic Cancer ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Differential Expression ◽  
A Genome

Abstract Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a “CNS signature.” Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true “CNS signature” because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

scholarly journals Primary Central Nervous System Lymphoma: Diffuse Large B-Cell Lymphoma

2019 ◽  
Vol 25 (4) ◽  
pp. 239-242
Author(s):  
Asuman Ali ◽  
Cemile Haki ◽  
Fatma Öz Atalay ◽  
Ramazan Yalçın
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3140-3146 ◽  
Author(s):  
Alexander Baraniskin ◽  
Jan Kuhnhenn ◽  
Uwe Schlegel ◽  
Andrew Chan ◽  
Martina Deckert ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Diagnostic Accuracy ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Diagnostic Value ◽  
Rna Molecules ◽  
Noninvasive Biomarker ◽  
The Central Nervous System

Abstract The diagnosis of primary central nervous system lymphoma (PCNSL) depends on histopathology of brain biopsies, because disease markers in the cerebrospinal fluid (CSF) with sufficient diagnostic accuracy are not available yet. MicroRNAs (miRNAs) are regulatory RNA molecules that are deregulated in many disease types, including cancer. Recently, miRNAs have shown promise as markers for cancer diagnosis. In this study, we demonstrate that miRNAs are present in the CSF of patients with PCNSL. With a candidate approach and miRNA quantification by reverse transcription polymerase chain reaction, miRNAs with significant levels in the CSF of patients with PCNSL were identified. MiR-21, miR-19, and miR-92a levels in CSF collected from patients with PCNSL and from controls with inflammatory CNS disorders and other neurologic disorders indicated a significant diagnostic value of this method. Receiver-operating characteristic analyses showed area under the curves of 0.94, 0.98, and 0.97, respectively, for miR-21, miR-19, and miR-92a CSF levels in discriminating PCNSL from controls. More importantly, combined miRNA analyses resulted in an increased diagnostic accuracy with 95.7% sensitivity and 96.7% specificity. We also demonstrated a remarkable stability of miRNAs in the CSF. In conclusion, CSF miRNAs are potentially useful tools as novel noninvasive biomarker for the diagnosis of PCNSL.

Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma

2020 ◽  
Vol 81 ◽  
pp. 72-75
Author(s):  
Junji Ikeda ◽  
Yasuhiro Shimojima ◽  
Tsuneaki Yoshinaga ◽  
Minori Kodaira ◽  
Sayaka Nishina ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
B Cell ◽  
Therapeutic Response ◽  
Cell Lymphoma ◽  
B Cell Lymphoma
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