Article
Medicine, General & Internal
Andrea Knight, Lucie Rihova, Romana Kralova, Miroslav Penka, Zdenek Adam, Ludek Pour, Martin Piskacek, Roman Hajek
Summary: The study revealed a significant reduction of pDCs in multiple myeloma patients, while pDCs were found to promote proliferation of MM cells and secrete IFN alpha. These results highlight the role of pDCs in MGUS and MM patients and their potential impact on immune function and treatment outcomes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Stefan Forster, Ramin Radpour, Adrian F. Ochsenbein
Summary: Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells in the bone marrow. The interaction between myeloma cells and the tumor microenvironment (TME) plays a crucial role in MM progression. Understanding the molecular mechanisms that drive MM and therapy resistance is essential for developing successful therapies and preventing MM recurrence. This review summarizes key mechanisms and emerging therapies in MM, including autocrine signaling, interactions with TME, and drug-resistance mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleksander Salomon-Perzynski, Joanna Barankiewicz, Marcin Machnicki, Irena Misiewicz-Krzeminska, Michal Pawlak, Sylwia Radomska, Agnieszka Krzywdzinska, Aleksandra Bluszcz, Piotr Stawinski, Malgorzata Rydzanicz, Natalia Jakacka, Iwona Solarska, Katarzyna Borg, Zofia Spyra-Gorny, Tomasz Szpila, Bartosz Pula, Sebastian Grosicki, Tomasz Stoklosa, Rafal Ploski, Ewa Lech-Maranda, Jana Jakubikova, Krzysztof Jamroziak
Summary: Tracking genetic changes during multiple myeloma progression reveals different patterns of mutation evolution, with mutation loss pathway associated with better treatment response. Many druggable genes are mutated, even in heavily pre-treated patients. Redefining R-ISS at relapse is clinically valuable.
Review
Medicine, General & Internal
Aleksander Salomon-Perzynski, Krzysztof Jamroziak, Eliza Glodkowska-Mrowka
Summary: Plasma cell dyscrasias are a heterogeneous group of diseases characterized by expansion of bone marrow plasma cells. Malignant transformation depends on a sequence of well-defined disease stages and requires development of multiple driver lesions, leading to genetically complex tumors that are difficult to treat. Understanding the mechanisms underlying tumor evolution and identifying mutations driving this evolution are crucial for effective treatment and disease control.
Article
Hematology
Normann Steiner, Georg Goebel, Daniela Michaeler, Anna-Luise Platz, Wolfgang Prokop, Anna Maria Wolf, Dominik Wolf, Christina Duftner, Eberhard Gunsilius
Summary: Chronic inflammatory diseases, especially non-antibody-mediated diseases, double the risk of progression from MGUS to overt multiple myeloma. Comorbidities like rheumatic diseases may need to be considered in MGUS prognostic scores.
Article
Oncology
Sarah Sandmann, Katharina Karsch, Peter Bartel, Rita Exeler, Tobias J. J. Brix, Elias K. K. Mai, Julian Varghese, Georg Lenz, Cyrus Khandanpour
Summary: In multiple myeloma, clonal evolution is associated with disease progression and treatment response.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuanzheng Liang, Haiyan He, Weida Wang, Henan Wang, Shaowen Mo, Ruiying Fu, Xindi Liu, Qiong Song, Zhongjun Xia, Liang Wang
Summary: This study establishes a global cell ecological landscape of bone marrow in multiple myeloma (MM) patients using single-cell RNA sequencing and single-molecule long-read genome sequencing data. The findings reveal the interaction between malignant clonal evolution pattern and tumor microenvironment in MM.
Review
Medicine, General & Internal
Niels W. C. J. van de Donk, Charlotte Pawlyn, Kwee L. Yong
Summary: Multiple myeloma is the second most common haematological malignancy in high-income countries. Current treatment strategies have extended patient survival, but the majority will ultimately die from the disease. Diagnostics and risk stratification are crucial for prognosis and treatment strategies.
Review
Biochemistry & Molecular Biology
Ivana Lagreca, Giovanni Riva, Vincenzo Nasillo, Patrizia Barozzi, Ilaria Castelli, Sabrina Basso, Francesca Bettelli, Davide Giusti, Angela Cuoghi, Paola Bresciani, Andrea Messerotti, Andrea Gilioli, Valeria Pioli, Corrado Colasante, Daniela Vallerini, Ambra Paolini, Monica Maccaferri, Francesca Donatelli, Fabio Forghieri, Monica Morselli, Elisabetta Colaci, Giovanna Leonardi, Roberto Marasca, Leonardo Potenza, Rossella Manfredini, Enrico Tagliafico, Tommaso Trenti, Patrizia Comoli, Mario Luppi
Summary: Multiple myeloma is a malignant growth of clonal plasma cells, and the immune system plays a significant role in the progression of the disease. This review focuses on the contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias, particularly in the progression from MGUS to SMM and MM. The potential of T cell-based immunotherapeutic approaches in these settings is highlighted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
G. Agarwal, C. Milan, Z. Mohsin, S. Mahoney, G. White, P. Stevens, S. Connacher, P. Osborne, R. Eckert, R. Sadler, K. Ramasamy, M. K. Javaid
Summary: Universal myeloma screening within a Fracture Liaison Service identified undiagnosed myeloma in 1 in 195 patients and precursor MGUS in 1 in 13 patients, potentially improving outcomes for patients and providing better treatment options. Further analysis with long-term follow-up is necessary to determine the true value of diagnosing MGUS within this setting and to assess the benefits versus costs of implementing such screening programs.
OSTEOPOROSIS INTERNATIONAL
(2022)
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
Oncology
Anastasios Tentolouris, Ioannis Ntanasis-Stathopoulos, Evangelos Terpos
Summary: Obesity is associated with various types of cancer, cardiovascular disease, and type 2 diabetes mellitus. This review focuses on exploring the relationship between obesity and multiple myeloma (MM), examining the impact of obesity on MM outcomes, investigating the mechanisms linking obesity to MM development, and discussing the effects of obesity management on MM. Current evidence suggests that obesity may contribute to the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM and increase the prevalence of MM. However, further research is required to clarify the effect of obesity on MGUS incidence. BMI is inversely correlated with survival in MM patients, but limited data are available on the effect of obesity on newly diagnosed MM subjects and autologous stem cell transplantation.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Leo Rasche, Carolina Schinke, Francesco Maura, Michael A. Bauer, Cody Ashby, Shayu Deshpande, Alexandra M. Poos, Maurizio Zangari, Sharmilan Thanendrarajan, Faith E. Davies, Brian A. Walker, Bart Barlogie, Ola Landgren, Gareth J. Morgan, Frits van Rhee, Niels Weinhold
Summary: By performing spatial-longitudinal whole-exome sequencing on multiple myeloma patients, the authors identified three evolutionary patterns and observed the presence of resistant sub-clones hidden over years. These findings provide insights into the evolution and treatment resistance of multiple myeloma, which are crucial for developing curative strategies.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Kazuhito Suzuki, Kaichi Nishiwaki, Shingo Yano
Summary: Multiple myeloma is an incurable hematological malignancy due to acquired drug resistance. Microenvironment and clonal evolution contribute to the development of de novo and acquired drug resistance in myeloma cells. Treatment with proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and autologous stem cell transplantation has improved prognosis by enhancing the bone marrow microenvironment. Initial treatment is crucial in addressing both types of drug resistance and should include a combination of these agents. This review highlights the importance of anti-myeloma agents in targeting the microenvironment and clonal evolution to overcome drug resistance.
Article
Hematology
Zhi Wen, Adhithi Rajagopalan, Evan D. Flietner, Grant Yun, Marta Chesi, Quinlan Furumo, Robert T. Burns, Athanasios Papadas, Erik A. Ranheim, Adam C. Pagenkopf, Zachary T. Morrow, Remington Finn, Yun Zhou, Shuyi Li, Xiaona You, Jeffrey Jensen, Mei Yu, Alexander Cicala, James Menting, Constantine S. Mitsiades, Natalie S. Callander, P. Leif Bergsagel, Demin Wang, Fotis Asimakopoulos, Jing Zhang
Summary: NRAS Q61 mutations are prevalent in advanced/relapsed multiple myeloma, with poor patient outcomes. A novel MM model was generated in mice, exhibiting characteristics similar to human advanced/high-risk MM. MEK inhibition-based therapies significantly prolonged survival in advanced-stage MM mice, suggesting potential for future clinical application.