scholarly journals MiRNA-223-3p Affects Mantle Cell Lymphoma Development by Regulating the CHUK/NF-ƘB2 Signaling Pathway

2021 ◽  
Vol Volume 14 ◽  
pp. 1553-1564
Author(s):  
Jingjing Yuan ◽  
Qing Zhang ◽  
Shengsheng Wu ◽  
Suran Yan ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Mantle Cell

scholarly journals SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma

Blood ◽  
2014 ◽  
Vol 124 (14) ◽  
pp. 2235-2247 ◽  
Author(s):  
Jara Palomero ◽  
Maria Carmela Vegliante ◽  
Marta Leonor Rodríguez ◽  
Álvaro Eguileor ◽  
Giancarlo Castellano ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Tumor Angiogenesis ◽  
Cell Lymphoma ◽  
Key Points ◽  
Mantle Cell

Key Points SOX11 mediates regulation of angiogenesis via the PDGFA signaling pathway in MCL. SOX11-dependent increased angiogenesis contributes to a more aggressive MCL phenotype.

scholarly journals Targeting the PI3K/Akt/mTOR signaling pathway by pterostilbene attenuates mantle cell lymphoma progression

2018 ◽  
Vol 50 (8) ◽  
pp. 782-792 ◽  
Author(s):  
Dandan Yu ◽  
Yong Zhang ◽  
Gege Chen ◽  
Yongsheng Xie ◽  
Zhijian Xu ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Mantle Cell

FAM19A5/S1PR1 signaling pathway regulates the viability and proliferation of mantle cell lymphoma

2021 ◽  
pp. 1-5
Author(s):  
Yanfang Wang ◽  
Zhenhao Zhang ◽  
Wei Wan ◽  
Yan Liu ◽  
Hongmei Jing ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Mantle Cell

scholarly journals Wogonin Inhibits Growth of Mantle Cell Lymphoma Cells through Nuclear Factor-κB Signaling Pathway

2018 ◽  
Vol 131 (4) ◽  
pp. 495-497 ◽  
Author(s):  
Pei-Pei Xu ◽  
Hua-Qin Zuo ◽  
Rong-Fu Zhou ◽  
Bing Chen ◽  
Jian Ouyang
Keyword(s):  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Lymphoma Cells ◽  
Mantle Cell

scholarly journals Inhibiting the Hippo Signaling Pathway Key Molecule YAP Suppresses Mantle Cell Lymphoma Proliferation By Regulating Multiple Pathogenrelated Signaling Pathways

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2566-2566
Author(s):  
Wenjie Xiong ◽  
Shuhua Yi ◽  
Yuting Yan ◽  
Zengjun Li ◽  
Wei Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mantle Cell Lymphoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
G1 Phase ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Mantle Cell ◽  
The Relationship

Object: Mantle cell lymphoma (MCL) is a rare hematologic malignancy with heterogeneous course and always resistant to chemotherapy at advance or relapsed stage. Hippo signaling pathway is one of the most popular pathways in solid tumors. The major role of this pathway is regulating cell proliferation, migration, and maintaining the stemness of cells. However, the relationship between this pathway and MCL had been rarely studied. The purpose of this study is to investigate the relationship between MCL and YAP, the key molecule Hippo signaling pathway, to further clarify the mechanism of MCL resistance and to find new therapeutic targets. Methods: In this study, expression of YAP in B cell non-hodgkin's lymphoma (B-NHL) and mantle cell lymphoma detected by real-time PCR, Western blot analysis, immunofluorescence. Knockdown of YAP by sh-RNA or inhibit the function of YAP using verteporfin (VP). Next, the effects of YAP knockdown and YAP inhibitor on MCL cells were evaluated by fluorescence detection, real-time PCR and Western blot. Cell count, CCK8, Soft Agar Assay and in vitro functional assays were performed to elucidate the function of YAP-mediated cell proliferation, the effect on signaling pathway and the relationship with chemoresistance in MCL. Results: We detected the expression of YAP in 40 B-NHL patients and 10 healthy donor and found that YAP were overexpressed in relapsed and newly diagnosis patients and it was extremely higher in relapsed patients. Moreover, YAP is extremely high express on MCL. Knockdown YAP by shRNA or YAP inhibitor verteporfin (VP) could not only inhibit the proliferation, induce the apoptosis of MCL cell lines, but also lead to cells stopping in G1 phase. In addition, knockdown YAP could sensitize Z138 cells to the cytotoxics of BTK inhibitors ibrutinib and SYK inhibitor R788.Combined VP and ibrutinib or R788 had obvious synergy. Most importantly, knockdown YAP could obviously reduce the expression of protein involved in G1 phase, inhibit the BCR signaling pathway and PI3K AKT signaling pathway, and promote cell apoptosis and DNA damage signaling pathways. Through regulating multiple signaling pathways, YAP played an important role in cell proliferation and drug resistance in B-NHL. Conclusion: It was the first time to demonstrate that Hippo signaling pathways may associate with the pathogenesis and drug resistance of MCL. Targeting the key molecular of Hippo signaling pathways may be potential therapeutic targets of MCL patients especially the relapse and refractory patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Anti-Leprosy Drug Clofazimine Synergizes with BTK Inhibitors and Proteasome Inhibitors in Drug-Resistant Mantle Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1190-1190
Author(s):  
Sayak Chakravarti ◽  
Harish Kumar ◽  
Suman Mazumder ◽  
Sabyasachi Sanyal ◽  
Brian G. Van Ness ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Therapeutic Options ◽  
Model Systems ◽  
Molecular Networks ◽  
Protein Ubiquitination ◽  
Mantle Cell

Abstract Mantle Cell Lymphoma (MCL) is a difficult to cure, highly heterogeneous, and aggressive form of non-Hodgkin lymphoma comprising roughly 7% of all cases with a high recurrence rate and poor long-term prognosis. The reported progression-free survival is about 1-2 years, and median overall survival/OS <3 years. Current first-line MCL therapies include combination regimens like R-CHOP, R-DHAP, Hyper-CVAD, VcR-CAP, etc. However, although patients respond well to initial treatment, most eventually progress to relapsed disease state. BTKis (Bruton's tyrosine kinase inhibitors) such as Ibrutinib are standard targeted therapeutic options for refractory or relapsed (R/R) MCL. The proteasome inhibitor (PI) drug Bortezomib/Velcade/Bz is another FDA-approved targeted drug for R/R MCL. However, despite these recent advances in the treatment landscape, R/R MCL still remains incurable with limited therapeutic options and a median OS<10-15 months. Therefore, there is an unmet need to discover novel drugs against R/R MCL. Previously, we have demonstrated that Clofazimine (CLF), an anti-leprosy drug, could potentially be repurposed for the treatment of chronic myeloid leukemia and PI/IMiD resistant multiple myeloma that also targets subclones representing putative stem-like-cells (CSCs). Notably, using single-cell analysis and high dimensional immunophenotyping or CyTOF (Cytometry Time of Flight), we have also identified molecular networks underpinning CLF+PI synergy. We hypothesize that CLF has strong potential to be repurposed as a novel anti-MCL drug, particularly in a relapsed/refractory setting. For this purpose, we used MCL cell lines representing drug-sensitive (JEKO1, MINO), innate PI/BTKi-resistance (Z138; representing refractory patients), and clonally-derived acquired PI/BTKi-resistance (MINO-R; representing relapse patients) as in vitro model systems and showed i) the efficacy of CLF as a single agent (IC 50= 6.9±3.6 uM) and ii) in combination with PIs (Bz) and BTKis (Ibrutinib, Acalabrutinib) against innate and acquired resistant MCL (Fig.1), as well as iii) the unique targeting of putative CSCs by CLF. Remarkably, CLF+BTKi/PI combination lowered the effective BTKi and PI doses required to achieve desired therapeutic response by >10-folds (estimated dose reduction index for BTKi and PI were 12.43 and 10.99, respectively). Further, mRNA-sequencing followed by differential gene expression analysis using DESeq2 and EdgeR revealed that the top significantly upregulated genes following PI+CLF treatment were GSR, DAP3, and DOK1, which have reported anti-tumorigenic activity. The top significantly downregulated genes EHD1, CBX8, DDX17, SOX12, and COMMD3 have reported pro-survival function. Ingenuity pathway analysis revealed protein ubiquitination pathway and cell cycle arrest at the G2/M phase as the top canonical pathways. Causal network analysis showed synergistic drug action significantly elevated the levels of oxidative stress and unfolded protein response. Additionally, PI+CLF combination potentiated AMPK mediated down-regulation of the mTOR signaling pathway, which further led to direct reduction of Cyclin D1 (aberrantly expressed in MCL) and the downregulation of eIF4-p70S6K signaling. The synergistic drug activity also led to the downregulation of oncogenic pathways like p38 MAPK and NF-kB signaling. Recent studies have indicated that intra-tumor heterogeneity due to the presence of stem-like cells in MCL (MCL-CSCs), including CD45+CD19- MCL-initiating cells (MCL-ICs), relatively quiescent-highly clonogenic aldehyde dehydrogenase (ALDH)+ cells and side populations (SP) may drive drug resistance and disease relapse. Notably, we found that several of the differentially regulated genes are critical for the maintenance and functioning of CSCs. For example, PI+CLF combination downregulates Wnt/β catenin signaling, which is found to be frequently overexpressed in MCL-ICs. HIPPO, another signaling pathway involved in the maintenance of cancer stem-ness and emergence of drug resistance, was also down-regulated. Currently, we are validating the specific targeting of putative MCL-CSCs by CLF. Next, we plan to replicate our findings using PDX models of MCL. CLF is an FDA-approved drug as well as on WHO's List of Essential Medicines. Thus, our study introduces CLF as a novel, safe, and inexpensive therapeutic option for the management of R/R MCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document