Article
Biochemistry & Molecular Biology
Hideki Kosako, Yusuke Yamashita, Shuhei Morita, Sadahiro Iwabuchi, Shinichi Hashimoto, Taka-Aki Matsuoka, Takashi Sonoki, Shinobu Tamura
Summary: This study found that activation of the endoplasmic reticulum stress pathway through modulation of c-Abl protein conformation can have anti-myeloma effects. Asciminib, a new allosteric c-Abl inhibitor, decreased cell viability and induced cell death in myeloma cells. This research provides a novel therapeutic target and potential treatment for multiple myeloma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Alexander Vdovin, Tomas Jelinek, David Zihala, Tereza Sevcikova, Michal Durech, Hana Sahinbegovic, Renata Snaurova, Dhwani Radhakrishnan, Marcello Turi, Zuzana Chyra, Tereza Popkova, Ondrej Venglar, Matous Hrdinka, Roman Hajek, Michal Simicek
Summary: Development of proteasome inhibitor resistance is a common problem in patients with multiple myeloma. The authors show that deubiquitinase OTUD1 protects PRDX4 from degradation, resulting in increased load of misfolded immunoglobulins and sensitizing myeloma cells for proteasome inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Zeinab Waad Sadiq, Annamaria Brioli, Ruba Al-Abdulla, Gonca Cetin, Jacqueline Schuett, Hugo Murua Escobar, Elke Krueger, Frederic Ebstein
Summary: This study investigates the effects of protein homeostasis disruptors on multiple myeloma cells and shows that inhibition of protein de-ubiquitination can induce immunogenic cell death, suggesting a new therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Magdalena Gebert, Jakub Slawski, Leszek Kalinowski, James F. Collawn, Rafal Bartoszewski
Summary: Efficient brain function requires a significant amount of oxygen intake, which can lead to oxidative stress and neurodegenerative diseases. The regulation of oxygen homeostasis and redox balance in the brain is mediated by stress response pathways, including the unfolded protein response (UPR). Understanding the opposing roles of UPR signaling pathways could provide insights for preventing cognitive decline and treating neurodegenerative diseases.
Article
Oncology
Elia Ranzato, Gregorio Bonsignore, Simona Martinotti
Summary: Malignant mesothelioma is a rare and aggressive cancer strongly linked to asbestos exposure. With limited therapeutic options, novel approaches are urgently needed. Previous studies have shown the importance of GRP78 in MPM survival, and our research suggests that BOLD-100, a specific modulator of GRP78, inhibits MPM cell growth by inducing cellular stress and cell death.
Review
Oncology
Guangqi Wang, Fengjuan Fan, Chunyan Sun, Yu Hu
Summary: This article summarizes the issues of relapses and drug resistance in the treatment of multiple myeloma (MM) patients and discusses novel therapeutic strategies to improve clinical outcomes by targeting endoplasmic reticulum stress (ERS) response.
Article
Biology
James P. Held, Gaomin Feng, Benjamin R. Saunders, Claudia Pereria, Kristopher Burkewitz, Maulik R. Patel, Xiaochen Wang
Summary: Researchers have discovered a new RNA-based cellular pathway, mediated by the enzyme HOE-1, that activates the mitochondrial unfolded protein response (UPRmt) by regulating the transcription factors ATFS-1 and DVE-1. This pathway does not rely on the integrated stress response and is likely mediated by tRNAs. The subcellular localization of HOE-1 is responsive to mitochondrial stress and is negatively regulated by ATFS-1.
Review
Biochemistry & Molecular Biology
Sinan Xiong, Wee-Joo Chng, Jianbiao Zhou
Summary: In multiple myeloma, cells experience both endoplasmic reticulum stress and oxidative stress, leading to cell fate decision through common signaling pathways and inter-organelle communication, ultimately resulting in apoptosis. The mutual activation between endoplasmic reticulum stress and oxidative stress forms a self-perpetuating cycle, contributing to the understanding of MM pathogenesis and drug resistance. Research focusing on targeting redox signaling and endoplasmic reticulum stress responses is highlighted for future anti-myeloma therapy development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Cell Biology
Zixin Zhou, Yumei Fan, Ruikai Zong, Ke Tan
Summary: Mitochondria are involved in various cellular functions and are regulated by the mitochondrial unfolded protein response (UPRmt) in response to environmental stresses. The regulatory mechanisms and factors involved in UPRmt differ between Caenorhabditis elegans and mammals. Exploring UPRmt can provide new directions and strategies for the treatment of human diseases.
AGEING RESEARCH REVIEWS
(2022)
Article
Oncology
Keiji Kurata, Anna-James Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
Summary: Multiple myeloma (MM) is a plasma cell malignancy associated with aberrant immunoglobulin production and proteotoxic stress. In this study, we identified glutamyl-prolyl-tRNA synthetase (GluProRS) as a potential therapeutic target. By developing a novel inhibitor called NCP26, we demonstrated its significant anti-tumour activity in various in vitro and in vivo systems, overcoming metabolic adaptation observed with other inhibitors. Our findings suggest a complex pro-apoptotic response beyond the integrated stress response, involving downregulated proline-rich motif-containing proteins as downstream effectors and establishing a novel determinant in MM pathobiology.
BLOOD CANCER JOURNAL
(2023)
Article
Environmental Sciences
Tianjin Lin, Gaohui Nie, Ruiming Hu, Junrong Luo, Chenghong Xing, Guoliang Hu, Caiying Zhang
Summary: Co-exposure of excess molybdenum (Mo) and cadmium (Cd) may induce autophagy in duck brain through disrupting calcium homeostasis and activating unfolded protein response (UPR).
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Public, Environmental & Occupational Health
Wen Xie, Rui Xu, Caiyun Fan, Chunyu Yang, Haiyan Chen, Yi Cao
Summary: Exposure to 900 MHz radiofrequency fields can increase ROS levels and induce a transient UPRmt in BMSC cells, which is reversed within 24 hours post-exposure. More research is needed to understand the detailed molecular mechanisms of RF-induced UPRmt.
FRONTIERS IN PUBLIC HEALTH
(2021)
Article
Multidisciplinary Sciences
Aditi Sharma, Remya Nair, Abhinav Achreja, Anjali Mittal, Pulkit Gupta, Kamakshi Balakrishnan, Claudia L. Edgar, Olamide Animasahun, Bhakti Dwivedi, Benjamin G. Barwick, Vikas A. Gupta, Shannon M. Matulis, Manoj Bhasin, Sagar Lonial, Ajay K. Nooka, Arun P. Wiita, Lawrence H. Boise, Deepak Nagrath, Mala Shanmugam
Summary: This study reveals the link between metabolic state and therapy resistance in multiple myeloma. Suppression of the electron transport chain increases resistance to proteasome inhibitors. Mitochondrial stress-induced resistance can be alleviated by specific drugs.
Article
Oncology
Yike Wan, Mengping Chen, Xin Li, Lu Zhong, Fei Xiao, Jia Liu, Jing Xiang, Jinxing Jiang, Xiaotong Chen, Junling Liu, Hua Li, Bin Li, Honghui Huang, Jian Hou
Summary: Single-cell RNA sequencing was used to compare gene expression profiles in T cells in bone marrow and peripheral blood of MM patients and healthy donors. The study revealed increased expression of senescence and exhaustion-related markers in cytotoxic T cells in MM. Pathway enrichment analyses showed downregulated amino acid metabolism, upregulated unfolded protein response pathways, and dysregulation of glutamine uptake in MM cytotoxic T cells.
Article
Multidisciplinary Sciences
Kristin Roseth Aass, Tonje Marie Vikene Nedal, Synne Stokke Tryggestad, Einar Haukas, Tobias S. Slordahl, Anders Waage, Therese Standal, Robin Mjelle
Summary: In this study, functional miRNA-mRNA target pairs were identified by analyzing miRNA and mRNA data from primary multiple myeloma cells. The study found that miRNA-mRNA pairs predicted by target-prediction algorithms were negatively correlated, indicating functional miRNA targeting. Furthermore, the study identified several target pairs associated with important processes in multiple myeloma, such as autophagy and protein degradation. These findings provide a knowledge base for further research in the miRNA/multiple myeloma field.
SCIENTIFIC REPORTS
(2022)
Review
Oncology
Irene Ghobrial, Calixto Hernandez Cruz, Alfred Garfall, Nina Shah, Nikhil Munshi, Jonathan Kaufman, Lawrence H. Boise, Gareth Morgan, Viktor A. Adalsteinsson, Salomon Manier, Rathi Pillai, Fabio Malavasi, Sagar Lonial
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2019)
Article
Multidisciplinary Sciences
Benjamin G. Barwick, Paola Neri, Nizar J. Bahlis, Ajay K. Nooka, Madhav Dhodapkar, David L. Jaye, Craig C. Hofmeister, Jonathan L. Kaufman, Vikas A. Gupta, Daniel Auclair, Jonathan J. Keats, Sagar Lonial, Paula M. Vertino, Lawrence H. Boise
NATURE COMMUNICATIONS
(2019)
Review
Immunology
Benjamin G. Barwick, Vikas A. Gupta, Paula M. Vertino, Lawrence H. Boise
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Multidisciplinary Sciences
Richa Bajpai, Aditi Sharma, Abhinav Achreja, Claudia L. Edgar, Changyong Wei, Arusha A. Siddiqa, Vikas A. Gupta, Shannon M. Matulis, Samuel K. McBrayer, Anjali Mittal, Manali Rupji, Benjamin G. Barwick, Sagar Lonial, Ajay K. Nooka, Lawrence H. Boise, Deepak Nagrath, Mala Shanmugam
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Nisha S. Joseph, Jonathan L. Kaufman, Madhav Dhodapkar, Craig C. Hofmeister, Dhwani K. Almaula, Leonard T. Heffner, Vikas A. Gupta, Lawrence H. Boise, Sagar Lonial, Ajay K. Nooka
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Letter
Oncology
Roberto Mina, Nisha S. Joseph, Francesca Gay, Efstathios Kastritis, Maria Teresa Petrucci, Jonathan L. Kaufman, Vittorio Montefusco, Maria Gavriatopoulou, Francesca Patriarca, Paola Omede, Lawrence H. Boise, Maria Roussou, Nicola Giuliani, Stefania Oliva, Massimo Offidani, Angelo Belotti, David L. Jaye, Lorenzo De Paoli, Evangelos Terpos, Sagar Lonial, Mario Boccadoro, Ajay K. Nooka, Meletios A. Dimopoulos
BLOOD CANCER JOURNAL
(2020)
Article
Cell Biology
Adam Utley, Colin Chavel, Shivana Lightman, G. Aaron Holling, James Cooper, Peng Peng, Wensheng Liu, Benjamin G. Barwick, Catherine M. Gavile, Orla Maguire, Megan Murray-Dupuis, Cheryl Rozanski, Martha S. Jordan, Taku Kambayashi, Scott H. Olejniczak, Lawrence H. Boise, Kelvin P. Lee
Review
Oncology
James Ackley, Miguel Armenta Ochoa, Delta Ghoshal, Krishnendu Roy, Sagar Lonial, Lawrence H. Boise
Summary: Multiple myeloma is an incurable disease characterized by malignant plasma cells, making it a prime target for modern immune therapy. Immune therapy for multiple myeloma can be categorized into IMiDs, targeted antibodies, adoptive cell transfer therapies, and vaccines, all showing advancements in improving antitumor activity and specificity.
Editorial Material
Hematology
Timothy M. Schmidt, Lawrence H. Boise
Summary: In this study, the authors use multiomics analysis to identify a novel transcriptional network that is crucial for the poor outcomes associated with chromosome 1q amplification in multiple myeloma.
Article
Oncology
Tyler Moser-Katz, Catherine M. Gavile, Benjamin G. Barwick, Kelvin P. Lee, Lawrence H. Boise
Summary: Despite advances in multiple myeloma treatment, the disease remains incurable. This study reveals the role of CD86 cytoplasmic tail in trafficking CD86 to the cell surface and identifies SCRIB and DLG1 as important proteins for myeloma cell growth and survival.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Olayinka O. Adebayo, Eric B. Dammer, Courtney D. Dill, Adeyinka O. Adebayo, Saheed O. Oseni, Ti'ara L. Griffen, Adaugo Q. Ohandjo, Fengxia Yan, Sanjay Jain, Benjamin G. Barwick, Rajesh Singh, Lawrence H. Boise, James W. Lillard
Summary: This study investigates the molecular mechanisms underlying treatment failures in multiple myeloma using bioinformatic tools. Through gene co-expression network analysis, modules of genes associated with disease survival status were identified and crucial genes within these modules were further studied. The findings reveal the biological functions related to the risk of death in multiple myeloma, providing insights for improving treatment strategies for the disease.
Article
Medicine, Research & Experimental
Yixiang Li, Baotong Zhang, Lingwei Xiang, Siyuan Xia, Omer Kucuk, Xingming Deng, Lawrence H. Boise, Jin-Tang Dong
Article
Hematology
Yu-Hsiu T. Lin, Gregory P. Way, Benjamin G. Barwick, Margarette C. Mariano, Makeba Marcoulis, Ian D. Ferguson, Christoph Driessen, Lawrence H. Boise, Casey S. Greene, Arun P. Wiita
Article
Medicine, Research & Experimental
Jithendra Kini Bailur, Samuel S. McCachren, Deon B. Doxie, Mahesh Shrestha, Katherine Pendleton, Ajay K. Nooka, Natalia Neparidze, Terri L. Parker, Noffar Bar, Jonathan L. Kaufman, Craig C. Hofmeister, Lawrence H. Boise, Sagar Lonial, Melissa L. Kemp, Kavita M. Dhodapkar, Madhav Dhodapkar
Article
Cell Biology
Katelyn G. Ponder, Lawrence H. Boise
CELL DEATH DISCOVERY
(2019)