Article
Hematology
Swetha Kambhampati, Ying Sheng, Chiung-Yu Huang, Sophia Bylsma, Mimi Lo, Vanessa Kennedy, Kelsey Natsuhara, Thomas Martin, Jeffrey Wolf, Nina Shah, Sandy W. Wong
Summary: B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy is an effective treatment for relapsed refractory multiple myeloma. This study analyzed the infection outcomes of 55 MM patients treated with BCMA CAR-T and found that despite multiple risk factors, severe infections were relatively rare.
Article
Medicine, Research & Experimental
M. Hope Robinson, Nancy Y. Villa, David L. Jaye, Ajay K. Nooka, Alyssa Duffy, Samuel S. McCachren, Julia Manalo, Jeffrey M. Switchenko, Sierra Barnes, Sayalee Potdar, Maryam I. Azeem, Ava A. Horvat, Vaunita C. Parihar, Jingjing Gong, Yan Liang, Geoffrey H. Smith, Vikas A. Gupta, Lawrence H. Boise, Jonathan L. Kaufman, Craig C. Hofmeister, Nisha S. Joseph, Sagar Lonial, Kavita M. Dhodapkar, Madhav V. Dhodapkar
Summary: This study investigates the mechanisms underlying immune infiltration in human multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) using high-dimensional spatial analyses and in vitro and in vivo modeling. The results suggest that MM exhibits clustered tumor growth and spatial heterogeneity with the coexistence of T cell-rich and T cell-sparse regions, as well as areas of T cell exclusion. T cell entry into MM clusters is regulated by agonistic signals and CD2-CD58 interactions, and CLEC9A+ DCs play a role in marking the portals of entry for T cell infiltration.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Oncology
Almudena Garcia-Ortiz, Yaiza Rodriguez-Garcia, Jessica Encinas, Elena Maroto-Martin, Eva Castellano, Joaquin Teixido, Joaquin Martinez-Lopez
Summary: Multiple myeloma is a hematologic cancer characterized by clonal proliferation of plasma cells in the bone marrow, with disease progression influenced by the tumor microenvironment created by various cells and soluble factors. Understanding the elements that control the microenvironment could lead to better-targeted therapies for this incurable disease.
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
Engineering, Biomedical
Cha He, Manqi Zhang, Lingling Liu, Yuhang Han, Zhanxue Xu, Yue Xiong, Fuxia Yan, Dandan Su, Hongbo Chen, Yongjiang Zheng, Fang Cheng
Summary: In this study, the authors propose a strategy of using engineered nanovesicles to capture excessive cytokines in the bone marrow microenvironment, aiming to enhance the sensitivity of multiple myeloma cells to the anti-cancer drug bortezomib.
ACTA BIOMATERIALIA
(2022)
Review
Medicine, General & Internal
Jelena Bila, Eirini Katodritou, Margarita Guenova, Sandra Basic-Kinda, Daniel Coriu, Milena Dapcevic, Lejla Ibricevic-Balic, Arben Ivanaj, Oliver Karanfilski, Samo Zver, Meral Beksac, Evangelos Terpos, Meletios Athanassios Dimopoulos
Summary: The course of multiple myeloma is influenced by tumor microenvironment. Treatment modalities like bortezomib can impact TME and individual profiles of MM patients need to be considered for optimal treatment.
JOURNAL OF CLINICAL MEDICINE
(2021)
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)
Review
Hematology
Mehmet Kemal Samur, Raphael Szalat, Nikhil C. Munshi
Summary: Single-cell platforms have become the norm in many research fields, including multiple myeloma, due to the high cellular heterogeneity of the disease. The decreasing cost and increasing accessibility of single-cell platforms, combined with breakthroughs in obtaining multiomics data and analyzing it, have allowed important insights into MM pathogenesis, with further work to be done.
Review
Cell Biology
Ilaria Saltarella, Aurelia Lamanuzzi, Benedetta Apollonio, Vanessa Desantis, Giulia Bartoli, Angelo Vacca, Maria Antonia Frassanito
Summary: Extracellular vesicles play a crucial role in the pathogenesis of multiple myeloma, reshaping the tumor microenvironment and promoting disease progression. They impact bone disease, angiogenesis, immunosuppression, drug resistance, and have potential as new therapeutic agents and clinical biomarkers.
Article
Hematology
Christie P. M. Verkleij, Marloes E. C. Broekmans, Mark van Duin, Kristine A. Frerichs, Rowan Kuiper, A. Vera de Jonge, Martin Kaiser, Gareth Morgan, Amy Axel, Rengasamy Boominathan, Jocelyn Sendecki, Amy Wong, Raluca Verona, Pieter Sonneveld, Sonja Zweegman, Homer C. Adams, Tuna Mutis, Niels W. C. J. van de Donk
Summary: GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab demonstrates potent anti-myeloma activity, effectively killing MM cells with high GPRC5D expression levels, especially with high effector:target ratio. Combination therapy with daratumumab or pomalidomide enhances talquetamab-mediated lysis of primary MM cells in an additive fashion.
Article
Hematology
Camille V. Edwards, Hamza Hassan, Cenk Yildirim, Grace Ferri, Karina P. Verma, Mara E. Murray Horwitz, Nathanael R. Fillmore, Nikhil C. Munshi
Summary: By analyzing the absolute monocyte count (AMC) in patients with multiple myeloma (MM), it was found that abnormal count is associated with inferior overall survival (OS), suggesting its potential as a prognostic marker for risk stratification.
Article
Genetics & Heredity
William Pilcher, Beena E. Thomas, Swati S. Bhasin, Reyka G. Jayasinghe, Lijun Yao, Edgar Gonzalez-Kozlova, Surendra Dasari, Seunghee Kim-Schulze, Adeeb Rahman, Jonathan Patton, Mark Fiala, Giulia Cheloni, Taxiarchis Kourelis, Madhav V. Dhodapkar, Ravi Vij, Shaadi Mehr, Mark Hamilton, Hearn Jay Cho, Daniel Auclair, David E. Avigan, Shaji K. Kumar, Sacha Gnjatic, Li Ding, Manoj Bhasin
Summary: The cause of rapid progressing disease in multiple myeloma (MM) patients is still unclear, but it is related to the complex interactions with bone marrow cells and the microenvironment that supports tumor growth and drug resistance. A multi-center single-cell RNA sequencing study on MM patients revealed that rapid progressors had higher levels of exhausted CD8+ T-cells and tolerogenic macrophages, as well as activation of pro-proliferative signaling pathways. On the other hand, non-progressive patients had higher levels of immature B cells. These findings provide valuable insights into the different cell populations and pathways associated with rapid progressing and non-progressing MM.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Federica Plano, Emilia Gigliotta, Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Carlotta Santonocito, Manuela Ingrasci, Laura Di Carlo, Antonino Elia Augello, Maria Speciale, Candida Vullo, Cristina Rotolo, Giulia Maria Camarda, Nadia Caccamo, Serena Meraviglia, Francesco Dieli, Sergio Siragusa, Cirino Botta
Summary: Multiple myeloma (MM) is a hematologic malignancy characterized by a pro-inflammatory and immunosuppressive microenvironment. Ferritin, released by pro-inflammatory cells, contributes to ROS production and cellular damage. The study found that high ferritin levels were associated with worse prognosis in MM patients and correlated with systemic inflammation markers and specific bone marrow cell microenvironment. Bioinformatic analysis also revealed that ferritin biosynthesis gene expression signature was associated with poor outcome and specific immune cell profiles. These findings suggest that ferritin could be a potential target for improving MM patient outcome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Daniela N. Petrusca, Kelvin P. Lee, Deborah L. Galson
Summary: This review presents the recent progress in research on the biological implications of sphingolipid metabolism alterations in the regulation of myeloma development, including its roles in migration and adhesion, survival and proliferation, angiogenesis and invasion, as well as the role of sphingolipids as mediators of the immune response and drug resistance in MM.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Junqiang Lv, Hao Sun, Lixin Gong, Xiaojing Wei, Yi He, Zhen Yu, Lanting Liu, Shuhua Yi, Weiwei Sui, Yan Xu, Shuhui Deng, Gang An, Zhi Yao, Lugui Qiu, Mu Hao
Summary: This study used single-cell RNA sequencing to reveal the dynamic features of immune cells in MM patients and found that immune cells were activated in patients with low tumor cell infiltration but suppressed with elevated MM cell infiltration, facilitating MM escape from immune surveillance. Abnormal expression of PIM kinases, KLRB1, and KLRC1 was also involved in the dysfunction of immune cells in MM patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Debora Soncini, Claudia Martinuzzi, Pamela Becherini, Elisa Gelli, Samantha Ruberti, Katia Todoerti, Luca Mastracci, Paola Contini, Antonia Cagnetta, Antonella Laudisi, Fabio Guolo, Paola Minetto, Maurizio Miglino, Sara Aquino, Riccardo Varaldo, Daniele Reverberi, Matteo Formica, Mario Passalacqua, Alessio Nencioni, Antonino Neri, Mehmet K. Samur, Nikhil C. Munshi, Mariateresa Fulciniti, Roberto M. Lemoli, Michele Cea
Summary: Recent studies have found aberrant splicing in cancer cells and suggested it as a potential therapeutic strategy. This study evaluated the expression of spliceosome machinery components in multiple myeloma cells and found that modulating splicing can impair cell growth and survival. The findings suggest that targeting splicing could make multiple myeloma patients more vulnerable to BCL2 inhibitors.
Article
Chemistry, Medicinal
Jian-Fei Bai, Somi Reddy Majjigapu, Bernard Sordat, Sophie Poty, Pierre Vogel, Pilar Elias-Rodriguez, Antonio J. Moreno-Vargas, Ana T. Carmona, Irene Caffa, Moustafa Ghanem, Amr Khalifa, Fiammetta Monacelli, Michele Cea, Inmaculada Robina, Consuelo Gajate, Faustino Mollinedo, Axel Bellotti, Aimable Nahimana, Michel Duchosal, Alessio Nencioni
Summary: FK866, a known NAMPT inhibitor with anti-cancer activity, showed anti-proliferative activity in PDAC cell lines. By synthesizing FK866 analogues, we identified several compounds with potent cell growth inhibitory activity. The best compounds were benzamide analogues of FK866.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Chiara Giannotti, Andrea Massobrio, Luca Carmisciano, Alessio Signori, Armando Napolitano, Davide Pertile, Domenico Soriero, Mariya Muzyka, Luca Tagliafico, Andrea Casabella, Michele Cea, Irene Caffa, Alberto Ballestrero, Roberto Murialdo, Alice Laudisio, Raffaele Antonelli Incalzi, Stefano Scabini, Fiammetta Monacelli, Alessio Nencioni
Summary: This study aimed to investigate the effect of geriatric comanagement on clinical outcomes in older patients undergoing surgery for gastrointestinal cancer. The implementation of geriatric comanagement resulted in a significant reduction in grade IeV complications and 1-year readmissions in the perioperative period.
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
(2022)
Article
Medicine, General & Internal
Alberto Stefano Tagliafico, Clarissa Valle, Pietro Andrea Bonaffini, Ali Attieh, Matteo Bauckneht, Liliana Belgioia, Bianca Bignotti, Nicole Brunetti, Alessandro Bonsignore, Enrico Capaccio, Sara De Giorgis, Alessandro Garlaschi, Silvia Morbelli, Federica Rossi, Lorenzo Torri, Simone Caprioli, Simona Tosto, Michele Cea, Alida Dominietto
Summary: This study assessed the reliability of the myeloma spine and bone damage score (MSBDS) among readers with different levels of expertise and from different institutions. The results showed substantial agreement among the readers, confirming the potential of MSBDS for large-scale applications.
Article
Oncology
Lars Guelen, Thierry O. Fischmann, Jerelyn Wong, Smita Mauze, Marco Guadagnoli, Nikolina Babala, Jozef Wagenaars, Veronica Juan, David Rosen, Winnie Prosise, Maurice Habraken, Imke Lodewijks, Danling Gu, Judith Stammen-Vogelzangs, Ying Yu, Jeanne Baker, David Lutje Hulsik, Lilian Driessen-Engels, Dan Malashock, Joost Kreijtz, Astrid Bertens, Evert de Vries, Astrid Bovens, Arne Bramer, Yiwei Zhang, Richard Wnek, Sean Troth, Elliot Chartash, Konstantin Dobrenkov, Svetlana Sadekova, Andrea van Elsas, Jason K. Cheung, Laurence Fayadat-Dilman, Jannie Borst, Amy M. Beebe, Hans Van Eenennaam
Summary: MK-5890, a novel CD27 agonistic antibody, has the potential to complement PD-1 checkpoint inhibition in cancer immunotherapy and is currently undergoing clinical evaluation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Hematology
Antonio Sacco, Vanessa Desantis, Jon Celay, Viviana Giustini, Fabio Rigali, Francesco D. Savino, Michele Cea, Debora Soncini, Antonia Cagnetta, Antonio G. Solimando, Deborah D'Aliberti, Silvia Spinelli, Daniele Ramazzotti, Camillo Almici, Katia Todoerti, Antonino Neri, Antonella Anastasia, Alessandra Tucci, Marina Motta, Marco Chiarini, Yawara Kawano, Jose A. Martinez-Climent, Rocco Piazza, Aldo M. Roccaro
Summary: Recent investigations have shown that Waldenstrom macroglobulinemia (WM) exhibits an increased number of regulatory T cells (Tregs), and Tregs derived from patients with WM have a peculiar mRNA signature and functional phenotype. WM cells trigger significantly higher induction, expansion, and proliferation of Tregs compared to normal cells, especially in the context of CXCR4(C1013G)-mutated WM cells. CD40/CD40-ligand interaction is identified as an important axis supporting the interaction between WM cells and Tregs.
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
Biochemical Research Methods
Erik van Buijtenen, Wout Janssen, Paul Vink, Maurice J. M. Habraken, Laura J. A. Wingens, Andrea van Elsas, Wilhelm T. S. Huck, Jessie A. G. L. van Buggenum, Hans van Eenennaam
Summary: Researchers integrated multi-omics single-cell sequencing technologies with an in vitro differentiation method to analyze the phenotypic characteristics of individual cells, revealing differences in immunoglobulin subclass-specific surface markers, transcriptional profiles, and signaling transduction pathway components. They also identified differential expression and sensitivity to cytokine stimulation in different ASCs, highlighting the importance of SYK, NF-kappa B, and mTOR activity in plasma cell differentiation and IgG secretion. This multi-omics approach provides valuable insights into human ASCs in healthy and diseased samples, and offers a useful tool for identifying novel biomarkers and potential drug targets.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Multidisciplinary Sciences
Xin Lei, Indu Khatri, Tom de Wit, Iris de Rink, Marja Nieuwland, Ron Kerkhoven, Hans van Eenennaam, Chong Sun, Abhishek D. Garg, Jannie Borst, Yanling Xiao
Summary: Despite their low abundance, cDC1s play a crucial role in anti-cancer immunity and are positively associated with patient survival. This study demonstrates that contact with activated CD4(+) T-cells enables cDC1s to induce a CTL response. The transcriptomic signature of helped cDC1s correlates with tumor infiltration by CTLs, Thelper(h)-1 cells, and overall survival.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Arjan Kol, Xiaoyu Fan, Marta. A. A. Wazynska, Sander M. J. van Duijnhoven, Danique Giesen, Annechien Plat, Hans Van Eenennaam, Philip. H. H. Elsinga, Hans. W. W. Nijman, Marco de Bruyn
Summary: This study focuses on generating and radiolabeling monoclonal antibodies targeting human CD103 for non-invasive immune PET imaging, demonstrating their potential as biomarkers for effective anticancer immune responses. The results show high specificity and sensitivity of the CD103 immuno-PET tracers in visualizing T cell infiltration, indicating their suitability for future applications in cancer immunotherapy assessment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Astigiano, Francesco Piacente, Maria Elena Laugieri, Andrea Benzi, Christian A. A. Di Buduo, Carolina P. P. Miguel, Debora Soncini, Michele Cea, Antonella Antonelli, Mauro Magnani, Alessandra Balduini, Antonio De Flora, Santina Bruzzone
Summary: SIRT6, a member of the sirtuin family, plays an emerging role in anti-inflammatory processes in various diseases and cell types, including endothelial cells. Overexpression of SIRT6 in human umbilical vein endothelial cells (SIRT6+ HUVECs) was found to affect adhesion molecule levels and promote megakaryocyte proliferation and proplatelet formation. Furthermore, the pro-inflammatory activation of the ATP/purinergic axis was reduced in SIRT6+ HUVECs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Paulina Biniecka, Saki Matsumoto, Axel Belotti, Jessie Joussot, Jian Fei Bai, Somi Reddy Majjigapu, Paul Thoueille, Dany Spaggiari, Vincent Desfontaine, Francesco Piacente, Santina Bruzzone, Michele Cea, Laurent A. A. Decosterd, Pierre Vogel, Alessio Nencioni, Michel A. A. Duchosal, Aimable Nahimana
Summary: The newly synthesized NAMPT inhibitor JJ08 exhibits a broad anticancer activity in vitro by inhibiting NAD(+) and NADP(H), generating ROS, and inducing cell death. In a mouse xenograft model of human Burkitt lymphoma, JJ08 delays tumor growth and shows potential for further evaluation in hematological malignancies.
Article
Biochemistry & Molecular Biology
Pamela Becherini, Debora Soncini, Silvia Ravera, Elisa Gelli, Claudia Martinuzzi, Giulia Giorgetti, Antonia Cagnetta, Fabio Guolo, Federico Ivaldi, Maurizio Miglino, Sara Aquino, Katia Todoerti, Antonino Neri, Andrea Benzi, Mario Passalacqua, Alessio Nencioni, Ida Perrotta, Maria Eugenia Gallo Cantafio, Nicola Amodio, Antonio De Flora, Santina Bruzzone, Roberto M. Lemoli, Michele Cea
Summary: Cancer cells increase their dependency on NAD(+) biosynthesis to support growth and energy demands, making it a vulnerability that can be targeted for anti-cancer strategies. CD38, a NAD(+)-degrading enzyme, is crucial for anti-myeloma therapies and its upregulation induces intracellular NAD(+) depletion, impairing mitochondrial function and increasing oxidative stress. This study suggests that targeting CD38 and its metabolic effects could enhance the effectiveness of NAD(+)-lowering agents in treating multiple myeloma patients.
Letter
Hematology
Elisa Gelli, Debora Soncini, Pamela Becherini, Claudia Martinuzzi, Katia Todoerti, Antonia Cagnetta, Sara Aquino, Fabio Guolo, Maurizio Miglino, Santina Bruzzone, Alessio Nencioni, Antonino Neri, Roberto M. Lemoli, Michele Cea
Review
Medicine, General & Internal
Carola Riva, Chiara Vernarecci, Paola Minetto, Rayan Goda, Marco Greppi, Silvia Pesce, Maria Chies, Giada Zecchetti, Beatrice Ferro, Elena Maio, Michele Cea, Roberto Massimo Lemoli, Emanuela Marcenaro, Fabio Guolo
Summary: Despite advancements in conventional chemotherapy and targeted therapies, the survival rate for acute myeloid leukemia (AML) remains unsatisfactory, particularly for relapsed/refractory or elderly/unfit patients. Cellular therapy has shown promising results in other hematological malignancies but has not been approved for clinical use in AML. Cellular therapy could be a powerful alternative to stem cell transplantation for ineligible patients.
JOURNAL OF CLINICAL MEDICINE
(2023)