Article
Oncology
Yuanjiao Zhang, Xichao Yu, Rongze Sun, Jie Min, Xiaozhu Tang, Zigen Lin, Siyuan Xie, Xinying Li, Shengfeng Lu, Zhidan Tian, Chunyan Gu, Lesheng Teng, Ye Yang
Summary: This study found that SFRS8 is upregulated in multiple myeloma and is associated with poor prognosis. SFRS8 can promote the progression of myeloma by regulating the alternative splicing of CACYBP and promote osteoclast differentiation through exosomes. Targeting the SFRS8/CACYBP/beta-catenin axis may be a promising strategy for the diagnosis and treatment of multiple myeloma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Cell Biology
Xiaohua Liu, Yuxiang Du, Zhonghan Zhao, Jun Zou, Xiaojing Zhang, Lingli Zhang
Summary: White adipose tissue (WAT) functions as both an energy storage reservoir and a metabolically active endocrine organ. It can secrete various adipocytokines and synthesize and secrete exosomes, which play important roles in intercellular communication and physiological processes. The skeleton, on the other hand, acts as a protective organ, gives the body its shape, and is regulated by cytokines secreted by WAT. The link between WAT and bone lipid regulation has been identified, suggesting potential targets for treating skeletal diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Hematology
Eline Menu, Karin Vanderkerken
Summary: This review summarizes the role of exosomes in multiple myeloma (MM), including their involvement in osteolysis, angiogenesis, immune suppression, and drug resistance. Targeting exosome secretion could potentially block these processes. The review also discusses current treatment strategies to counter these processes and explores how exosomes can be harnessed to deliver toxic payloads. Additionally, the review provides an overview of clinical studies investigating exosome cargo as potential MM biomarkers in liquid biopsies.
Article
Oncology
Julia Dahlhoff, Hannah Manz, Tim Steinfatt, Julia Delgado-Tascon, Elena Seebacher, Theresa Schneider, Amy Wilnit, Zeinab Mokhtari, Paula Tabares, David Boeckle, Leo Rasche, K. Martin Kortuem, Manfred B. Lutz, Hermann Einsele, Andreas Brandl, Andreas Beilhack
Summary: This study found that Tregs accumulate near malignant plasma cells in the bone marrow of multiple myeloma patients and display an activated phenotype. Short-term depletion of Tregs in mouse models with established multiple myeloma led to a potent immune response mediated by CD8 T cells and NK cells, resulting in complete and stable remission. This preclinical in-vivo study suggests that Tregs may be a promising target for the treatment of multiple myeloma.
Review
Oncology
Timothy M. Schmidt, Rafael Fonseca, Saad Z. Usmani
Summary: +1q chromosome gain is common in multiple myeloma, often seen as a poor prognostic marker but not uniformly adopted as high-risk. Controversy exists regarding its importance, with many genes at the 1q21 locus proposed to cause resistance to therapy.
BLOOD CANCER JOURNAL
(2021)
Article
Hematology
Tomofumi Yamamoto, Jun Nakayama, Yusuke Yamamoto, Masahiko Kuroda, Yutaka Hattori, Takahiro Ochiya
Summary: This study reveals the molecular and cellular mechanisms of lenalidomide resistance in multiple myeloma (MM), showing that lenalidomide-resistant MM cells have enhanced extracellular vesicle (EV) secretion and adherence abilities. SORT1 and LAMP2 genes are identified as key regulators of EV secretion. Silencing of these genes decreases EV secretion and impairs cell adhesion in resistant cells, resulting in increased sensitivity to lenalidomide. Analysis of transcriptome data supports the relationship between genes related to EV secretion and adherence and patient prognosis.
Article
Hematology
Lea Lemaitre, Malik Hamaidia, Jean-Gerard Descamps, Laura Do Souto Ferreira, Marie-Veronique Joubert, Melanie Gadelorge, Herve Avet-Loiseau, Arthur Justo, Nicolas Reina, Frederic Deschaseaux, Ludovic Martinet, Philippe Bourin, Jill Corre, Nicolas Espagnolle
Summary: TLR4 gene is upregulated in abnormal BM mesenchymal stromal cells (MSCs) in multiple myeloma (MM), and its inhibition reduces MM cell growth and delays disease progression.
Article
Cell Biology
Yi Yao, Kalpana Subedi, Tingting Liu, Namir Khalasawi, Carla Diana Pretto-Kernahan, Jesse William Wotring, Jie Wang, Congcong Yin, Aimin Jiang, Chunmei Fu, Peter Dimitrion, Jia Li, Jesse Veenstra, Qijun Yi, Kathy McKinnon, John Ernest McKinnon, Jonathan Zachary Sexton, Li Zhou, Qing-Sheng Mi
Summary: It has been a topic of debate whether human peripheral blood cells can be infected by SARS-CoV-2, as immune cells do not express mRNA of both ACE2 and TMPRSS2. Here, the researchers demonstrate that resting primary monocytes contain abundant cytoplasmic ACE2 and TMPRSS2 proteins, and circulating exosomes contain significant ACE2 protein. Upon TLR4/7/8 stimulation, ACE2 quickly translocates to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurs with elevated mRNA expression. TLR-stimulated monocytes expressing both ACE2 and TMPRSS2 on the cell surface are efficiently infected by SARS-CoV-2, but this infection can be mitigated by drugs and antibodies. The study also shows that ACE2 surface translocation in peripheral myeloid cells from severe COVID-19 patients correlates with hyperactivation and PD-L1 expression.
Review
Oncology
Raquel Lopes, Bruna Velosa Ferreira, Joana Caetano, Filipa Barahona, Emilie Arnault Carneiro, Cristina Joao
Summary: Multiple myeloma is a hematological malignancy arising from the proliferation of tumor antibody-producing cells in the bone marrow. Immunotherapy is a form of cancer treatment that aims to stimulate the immune system to fight back tumor cells, but has not yet been able to cure multiple myeloma completely.
Article
Cell Biology
Yang Cao, Huizhuang Shan, Meng Liu, Jia Liu, Zilu Zhang, Xiaoguang Xu, Yue Liu, Hanzhang Xu, Hu Lei, Miao Yu, Xingming Zhang, Wanting Liu, Zhilei Bu, Zhixiao Fang, Yanjie Ji, Hua Yan, Weiying Gu, Yingli Wu
Summary: The study demonstrates that anlotinib exhibits significant anti-myeloma effects by inducing cell cycle arrest, apoptosis, and inhibiting multiple signaling pathways. Notably, it also targets c-Myc and enhances ubiquitin proteasomal degradation, leading to apoptosis. Additionally, anlotinib shows cytotoxicity against bortezomib-resistant MM cells, suggesting its potential clinical application for human MM treatment.
CELL DEATH & DISEASE
(2021)
Article
Endocrinology & Metabolism
Guoqing Zhu, Yanping Ma, Xue Fu, Xiaofei Ai, Gang An, Hui Cheng
Summary: This study evaluated the potential exosomal miRNAs and associated molecular mechanisms in multiple myeloma (MM). Through transcriptome sequencing of serum exosomes RNA, differentially expressed miRNAs and miRNA-mRNA interactions were identified. The study revealed the significance of salivary gland development and PI3K-Akt signaling pathway in MM progression, and suggested that exosome-derived miR-125b-5p and STAT3 in the SPACA6P-AS-miR-125b-5p-STAT3 axis could be potential biomarkers for MM.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Medicine, General & Internal
Ye Peng, Xiaolu Song, Jianping Lan, Xiaogang Wang, Manling Wang
Summary: Interaction with BMSCs and exosomes may play a vital role in the progression of MM. The study identified miR-10a and miR-16 as potential biomarkers for MM progression by regulating specific genes, suggesting their potential as therapeutic targets.
Article
Medicine, Research & Experimental
Chenggong Tu, Zhimin Du, Hui Zhang, Yueyuan Feng, Yujun Qi, Yongjiang Zheng, Jinbao Liu, Jinheng Wang
Summary: Extracellular vesicles derived from bone marrow stromal cells can promote the cycling of multiple myeloma cells and reduce their sensitivity to bortezomib. Inhibiting endocytosis can decrease vesicle uptake by cells and enhance the anti-myeloma effects of bortezomib.
Review
Oncology
Frances Seymour, Jonathan Carmichael, Claire Taylor, Christopher Parrish, Gordon Cook
Summary: Age-related immune dysfunction is primarily mediated by immunosenescence, leading to immunometabolic abnormalities, accelerated aging, inflammatory immune response, and frailty syndromes. Understanding the mechanisms of accelerated immunological aging and the influence of tumors like multiple myeloma is crucial for overcoming therapeutic barriers.
Article
Cell Biology
Danfeng Zhang, Jingcao Huang, Fangfang Wang, Hong Ding, Yushan Cui, Yan Yang, Juan Xu, Hongmei Luo, Yuhan Gao, Ling Pan, Yu Wu, Yuping Gong, Liping Xie, Zhigang Liu, Ying Qu, Li Zhang, Weiping Liu, Wenyan Zhang, Sha Zhao, Qing Yi, Ting Niu, Yuhuan Zheng
Summary: Multiple myeloma is a malignancy characterized by plasma cell accumulation in the bone marrow. Within the tumor microenvironment, macrophages in multiple myeloma exhibit pro-myeloma functions, which are modulated by the polycomb-group protein BMI1. Knockout of BMI1 in MM-associated macrophages leads to reduced proliferation, decreased expression of angiogenic factors, and loss of protection against chemotherapy-induced cell death, ultimately negating the pro-myeloma effects of these cells.
CELL DEATH & DISEASE
(2021)
Article
Engineering, Biomedical
Carolina Paganini, Britta Hettich, Marie R. G. Kopp, Adam Eordogh, Umberto Capasso Palmiero, Giorgia Adamo, Nicolas Touzet, Mauro Manno, Antonella Bongiovanni, Pablo Rivera-Fuentes, Jean-Christophe Leroux, Paolo Arosio
Summary: This microfluidic technique allows for rapid detection and quantification of components associated with EV subtypes and impurities, measuring EV purity in minutes with minimal sample handling and less than 5 μL of sample. It accelerates screening of EV samples, aids in evaluating sample reproducibility, and serves as an important complementary tool to current biophysical methods for EV characterization.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Biotechnology & Applied Microbiology
Sabrina Picciotto, Pamela Santonicola, Angela Paterna, Estella Rao, Samuele Raccosta, Daniele Paolo Romancino, Rosina Noto, Nicolas Touzet, Mauro Manno, Elia Di Schiavi, Antonella Bongiovanni, Giorgia Adamo
Summary: Extracellular vesicles (EVs) are lipid membrane nano-sized vesicles secreted by various cell types for intercellular communication. Nanoalgosomes, a subtype of EVs derived from microalgae, show potential as nanocarriers of bioactive compounds. In this study, it was found that nanoalgosomes can be actively uptaken in vitro by human cells and in vivo by C. elegans cells, offering potential applications for theranostics.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Oncology
Paola Storti, Valentina Marchica, Rosanna Vescovini, Valentina Franceschi, Luca Russo, Laura Notarfranchi, Vincenzo Raimondi, Denise Toscani, Jessica Burroughs Garcia, Federica Costa, Benedetta Dalla Palma, Nicolas Thomas Iannozzi, Gabriella Sammarelli, Gaetano Donofrio, Nicola Giuliani
Summary: The humoral and cellular response to SARS-CoV-2 vaccination is reduced in patients with multiple myeloma. Spike variants, especially Omicron, have a significant negative impact on the neutralizing ability of vaccine-induced antibodies. Heterologous booster immunization improves the response in newly diagnosed MM patients, but Omicron still poses challenges for patients with relapsed-refractory disease.
Review
Oncology
Vincenzo Raimondi, Denise Toscani, Valentina Marchica, Jessica Burroughs-Garcia, Paola Storti, Nicola Giuliani
Summary: Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) in the bone marrow (BM). The complex interaction between the BM microenvironment and MM cells has a significant impact on bone remodeling. MM cells exhibit metabolic alterations, including enhanced glycolysis and glutamine addiction, which can affect the differentiation process of bone cells. Understanding these metabolic changes may lead to the development of new therapeutic approaches and diagnostic tools for MM patients.
FRONTIERS IN ONCOLOGY
(2022)
Letter
Oncology
Laura Notarfranchi, Roberta Segreto, Rosanna Vescovini, Anna Benedetta Dalla Palma, Valentina Marchica, Jessica Burroughs-Garcia, Denise Toscani, Giannalisa Todaro, Vincenzo Raimondi, Nicolas Thomas Iannozzi, Sabrina Bonomini, Gabriella Sammarelli, Luisa Craviotto, Mario Pedrazzoni, Paola Storti, Nicola Giuliani
HEMATOLOGICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Nicolas Thomas Iannozzi, Valentina Marchica, Denise Toscani, Jessica Burroughs Garcia, Nicola Giuliani, Paola Storti
Summary: Multiple myeloma is characterized by unregulated proliferations of plasma cells in bone marrow, which is influenced by the bone marrow microenvironment. The alterations of mesenchymal stromal cells and osteoblasts in multiple myeloma patients contribute to myeloma-associated bone disease. Understanding the characteristics and molecular pathways of these cells can provide insights into the pathophysiology of multiple myeloma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Roberto Mina, Pellegrino Musto, Delia Rota-Scalabrini, Laura Paris, Barbara Gamberi, Angelo Palmas, Sara Aquino, Paolo de Fabritiis, Nicola Giuliani, Luca De Rosa, Alessandro Gozzetti, Claudia Cellini, Luca Bertamini, Andrea Capra, Daniela Oddolo, Iolanda Donatella Vincelli, Sonia Ronconi, Vincenzo Pavone, Norbert Pescosta, Michele Cea, Francesca Fioritoni, Stelvio Ballanti, Mariella Grasso, Elena Zamagni, Angelo Belotti, Mario Boccadoro, Francesca Gay
Summary: Maintenance treatment with carfilzomib plus lenalidomide for two years prolongs progression-free survival in patients with multiple myeloma. However, patients with two or more high-risk cytogenetic abnormalities still have an increased risk of progression and death.
Article
Materials Science, Biomaterials
Miriam Romano, Manuel Antonio Gonzalez Gomez, Pamela Santonicola, Noemi Aloi, Svenja Offer, Jana Pantzke, Samuele Raccosta, Valeria Longo, Alessandro Surpi, Silvia Alacqua, Giuseppina Zampi, Valentin Alek Dediu, Bernhard Michalke, Ralf Zimmerman, Mauro Manno, Yolanda Pineiro, Paolo Colombo, Elia Di Schiavi, Jose Rivas, Paolo Bergese, Sebastiano Di Bucchianico
Summary: The SPIONs@SiO2-PDA nanoplatform developed in this study exhibits excellent biocompatibility, effectively protecting SPIONs and providing enhanced colloidal stability.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2022)
Editorial Material
Hematology
Nicola Giuliani, Luisa Craviotto
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Oxana Lungu, Denise Toscani, Jessica Burroughs-Garcia, Nicola Giuliani
Summary: The study of osteoblast metabolism has attracted increasing attention recently due to its high energy demand during bone remodeling. In addition to glucose, recent data show that amino acid and fatty acid metabolism plays an important role in providing fuel for osteoblast functioning. Glutamine has been identified as a crucial amino acid for osteoblast differentiation and activity. This review focuses on the metabolic pathways involved in the fate and functions of osteoblasts, particularly in multiple myeloma (MM) bone disease where the presence of malignant plasma cells disrupts osteoblast formation and activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Oncology
Denise Toscani, Martina Chiu, Vincenzo Raimondi, Nicolas Thomas Iannozzi, Oxana Lungu, Jessica Burroughs Garcia, Laura Notarfranchi, Benedetta Anna Dalla Palma, Giuseppe Taurino, Ovidio Bussolati, Nicola Giuliani
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Hematology
J. Burroughs-Garcia, P. Storti, L. Agnelli, D. Toscani, V. Marchica, G. Sammarelli, G. Todaro, V. Raimondi, V. Franceschi, N. Soressi, B. Dalla Palma, L. Notarfranchi, G. Donofrio, N. Giuliani
Meeting Abstract
Hematology
L. Notarfranchi, P. Storti, R. Vescovini, R. Segreto, S. Bonomini, G. Sammarelli, G. Todaro, V. Raimondi, J. Burroughs-Garcia, D. Toscani, A. B. Dalla Palma, N. Giuliani
Meeting Abstract
Hematology
P. Storti, R. Vescovini, V. Marchica, V. Franceschi, V. Raimondi, N. Soressi, B. Dalla Palma, L. Notarfranchi, F. Falcioni, M. Giaimo, F. Costa, D. Toscani, J. Burroughs Garcia, G. Donofrio, N. Giuliani