Article
Oncology
Bachisio Ziccheddu, Matteo C. Da Via, Marta Lionetti, Akihiro Maeda, Silvia Morlupi, Matteo Dugo, Katia Todoerti, Stefania Oliva, Mattia D'Agostino, Paolo Corradini, Ola Landgren, Francesco Iorio, Loredana Pettine, Alessandra Pompa, Martina Manzoni, Luca Baldini, Antonino Neri, Francesco Maura, Niccolo Bolli
Summary: The study identified the impact of gene mutations, copy-number abnormalities, and chromosomal rearrangements on the transcriptome of multiple myeloma patients, revealing distinct effects on deregulated genes, pathways, and biomarkers for personalized treatments. Immunoglobulin translocations, hyperdiploidy, and chr(1q) gain/amps were found to have the highest association with deregulated genes. Mutations in oncogenes and inactivation of tumor suppressor genes had a significant impact on gene expression. Comprehensive analysis helps in identifying specific deregulated pathways and candidate biomarkers for personalized treatments in multiple myeloma.
CLINICAL CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Aristea-Maria Papanota, Paraskevi Karousi, Christos K. Kontos, Ioannis Ntanasis-Stathopoulos, Andreas Scorilas, Evangelos Terpos
Summary: Multiple myeloma (MM) is a common hematological malignancy characterized by bone disease resulting from imbalance in bone-remodeling process. miRNAs play a crucial role in the pathophysiology of MMBD and are potential molecular targets for targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Leora S. Boussi, Zachary M. Avigan, Jacalyn Rosenblatt
Summary: Despite advances in treatment for multiple myeloma, understanding the mechanisms of immune evasion and resistance to therapy is critical for developing more effective treatments. Cellular adoptive therapy, particularly CAR T cell therapy, has shown promising results in refractory cases and may be a viable option for treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Doris K. Hansen, Surbhi Sidana, Lauren C. Peres, Christelle Colin Leitzinger, Leyla Shune, Alexandria Shrewsbury, Rebecca Gonzalez, Douglas W. Sborov, Charlotte Wagner, Danai Dima, Hamza Hashmi, Mehmet H. Kocoglu, Shebli Atrash, Gary Simmons, Nilesh Kalariya, Christopher Ferreri, Aimaz Afrough, Ankit Kansagra, Peter Voorhees, Rachid Baz, Jack Khouri, Melissa Alsina, Joseph McGuirk, Frederick L. Locke, Krina K. Patel
Summary: A retrospective analysis showed that the safety and efficacy of standard-of-care ide-cel therapy in RRMM patients were similar to those seen in the phase II KarMMa trial, despite most patients not meeting the trial eligibility criteria.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Peter Neumeister, Eduard Schulz, Katrin Pansy, Marta Szmyra, Alexander Ja Deutsch
Summary: Multiple myeloma (MM) is a malignant and incurable disease characterized by the interaction between tumor cells and the bone marrow microenvironment. Therapeutic interventions targeting the bone marrow microenvironment have become a novel strategy for treating multiple myeloma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Health Care Sciences & Services
Alessandro Gozzetti, Monica Bocchia
Summary: The survival rate of multiple myeloma has increased in the past 20 years due to new treatments, improved clinical management, and a better understanding of the disease. Novel drugs and therapeutic strategies have allowed a considerable number of patients to achieve durable remission or even disease disappearance.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Natalia Platonova, Elisa Lazzari, Michela Colombo, Monica Falleni, Delfina Tosi, Domenica Giannandrea, Valentina Citro, Lavinia Casati, Domenica Ronchetti, Niccolo Bolli, Antonino Neri, Federica Torricelli, Leslie A. Crews, Catriona H. M. Jamieson, Raffaella Chiaramonte
Summary: The NOTCH ligands JAG1 and JAG2 have been linked to multiple myeloma (MM) cell proliferation, drug resistance, self-renewal, and communication with the tumor microenvironment. Targeting JAG1/2 shows potential as a therapeutic approach for MM. Silencing JAG1 and JAG2 leads to reduced tumor burden in a MM xenograft model, and their protein expression is correlated with the presence of MM cells in patients' bone marrow. Furthermore, JAG2 gene expression level serves as a predictive biomarker for overall survival and progression-free survival in MM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Danai Dima, Dongxu Jiang, Divya Jyoti Singh, Metis Hasipek, Haikoo S. Shah, Fauzia Ullah, Jack Khouri, Jaroslaw P. Maciejewski, Babal K. Jha
Summary: Multiple myeloma (MM) is a complex hematologic malignancy that remains incurable despite several therapeutic advancements. This review discusses the current treatment paradigm of MM and highlights promising future approaches.
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
Oncology
Craig T. Wallington-Beddoe, Rachel L. Mynott
Summary: New approaches are needed to stratify multiple myeloma patients based on prognosis and therapeutic decision-making, however, insufficient information currently exists to utilize biomarkers to tweak treatment. With the increasing complexity of drug classes used to treat multiple myeloma, clinically useful biomarkers are crucial in guiding personalized patient management.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemical Research Methods
Ziyang Ma, Jeongyoun Ahn
Summary: The study proposed a new method that can reveal the ordinal structure of classes in high-dimensional data and applied it to predict the response of multiple myeloma patients to different drugs. Comparative analysis with existing methods showed that the proposed method achieves competitive predictive performance while maintaining the intrinsic ordinal structure of classes.
Article
Hematology
Mohamad Mohty, Herve Avet-Loiseau, Jean-Luc Harousseau
Summary: With recent therapeutic advancements, operational cure for multiple myeloma is becoming a realistic goal. The correlation between MRD negativity and improved patient outcomes suggests MRD as a surrogate for potential long-term cure. Various parameters influence the value and impact of MRD, with different treatment approaches leading to potential operational cure in both younger and older patients.
Review
Hematology
Iuliana Vaxman, Morie A. Gertz
Summary: This review discusses the current standard of care for smoldering multiple myeloma and efforts to understand its progression to active multiple myeloma. Two patient cases are presented to illustrate that sometimes patients can undergo observation only, even when they exceed criteria for high-risk smoldering multiple myeloma.
Review
Oncology
Yushan Cui, Fujue Wang, Baijun Fang
Summary: Multiple myeloma (MM) is a commonly occurring hematological cancer without a cure. Drug resistance and disease relapse are major challenges in MM treatment. Aberrant mitochondrial function, including DNA mutations and metabolic reprogramming, has been observed in MM patients. Mitochondria-targeting therapies have shown promising results in preclinical and clinical studies. This review summarizes our current knowledge of mitochondrial biology in MM and discusses strategies for targeting mitochondria in MM treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Francesco Maura, Niels Weinhold, Benjamin Diamond, Dickran Kazandjian, Leo Rasche, Gareth Morgan, Ola Landgren
Summary: The identification of mutational processes in multiple myeloma, including a new mutational signature caused by exposure to high-dose melphalan, has been made possible through whole genome and exome sequencing. Exposure to high-dose melphalan increases mutational burden between diagnosis and relapse, with most mutations occurring in heterochromatin and late-replicating regions, rarely affecting key myeloma driver genes.
Review
Oncology
Tina Paradzik, Cecilia Bandini, Elisabetta Mereu, Maria Labrador, Elisa Taiana, Nicola Amodio, Antonino Neri, Roberto Piva
Summary: Recent investigations are exploring novel combination strategies that could overcome drug resistance and broaden the applicability of proteasome inhibitors (PIs) to other hematological malignancies and solid tumors.
Letter
Hematology
Fortunato Morabito, Giovanni Del Poeta, Francesca Romana Mauro, Gianluigi Reda, Paolo Sportoletti, Luca Laurenti, Marta Coscia, Yair Herishanu, Sabrina Bossio, Marzia Varettoni, Roberta Murru, Annalisa Chiarenza, Andrea Visentin, Adalgisa Condoluci, Riccardo Moia, Daniela Pietrasanta, Giacomo Loseto, Ugo Consoli, Ilaria Scortechini, Anna Grazia Recchia, Francesca Maria Rossi, Antonella Zucchetto, Hamdi Al-Janazreh, Enrica Antonia Martino, Ernesto Vigna, Giovanni Tripepi, Graziella D'Arrigo, Sara Galimberti, Angela Rago, Ilaria Angeletti, Annalisa Biagi, Ilaria Del Giudice, Riccardo Bomben, Antonino Neri, Gilberto Fronza, Giovanna Cutrona, Ozren Jaksic, Jacopo Olivieri, Davide Rossi, Francesco Di Raimondo, Antonio Cuneo, Gianluca Gaidano, Aaron Polliack, Livio Trentin, Robin Foa, Manlio Ferrarini, Valter Gattei, Massimo Gentile
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Letter
Hematology
Fortunato Morabito, Giovanni Tripepi, Giovanni Del Poeta, Francesca Romana Mauro, Gianluigi Reda, Paolo Sportoletti, Luca Laurenti, Marta Coscia, Yair Herishanu, Sabrina Bossio, Marzia Varettoni, Roberta Murru, Annalisa Chiarenza, Andrea Visentin, Adalgisa Condoluci, Riccardo Moia, Daniela Pietrasanta, Giacomo Loseto, Ugo Consoli, Ilaria Scortechini, Francesca Maria Rossi, Antonella Zucchetto, Hamdi Al-Janazreh, Ernesto Vigna, Enrica Antonia Martino, Ramona Cassin, Graziella DArrigo, Sara Galimberti, Angela Rago, Ilaria Angeletti, Annalisa Biagi, Ilaria Del Giudice, Riccardo Bomben, Antonino Neri, Gilberto Fronza, Paola Monti, Paola Menichini, Jacopo Olivieri, Giovanna Cutrona, Davide Rossi, Antonio Cuneo, Francesco Di Raimondo, Gianluca Gaidano, Aaron Polliack, Livio Trentin, Robin Foa, Manlio Ferrarini, Valter Gattei, Massimo Gentile
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Hematology
Katia Todoerti, Domenica Ronchetti, Vanessa Favasuli, Francesco Maura, Fortunato Morabito, Niccolo Bolli, Elisa Taiana, Antonino Neri
Summary: DIS3 gene mutations occur in a significant proportion of patients with multiple myeloma, particularly in relation to 13q abnormalities. These mutations have a significant impact on the clinical outcome, leading to poor prognosis in terms of progression-free survival and overall survival. Furthermore, DIS3 mutations affect RNA metabolism and the dysregulation of numerous long non-coding RNA, which could serve as independent predictors of unfavorable outcomes in MM patients.
Article
Oncology
Daniele Caracciolo, Caterina Riillo, Giada Juli, Francesca Scionti, Katia Todoerti, Nicoletta Polera, Katia Grillone, Lucia Fiorillo, Mariamena Arbitrio, Maria Teresa Di Martino, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone
Summary: The MYC-driven deregulation of microRNAs, particularly the repression of miR-22, plays a critical role in multiple myeloma (MM) and resistance to immunomodulatory imide drugs (IMiDs). Lenalidomide treatment enhances miR-22 activity by reducing MYC inhibition, which restores drug sensitivity and leads to synergistic anti-MM activity.
Article
Oncology
Fortunato Morabito, Giovanni Tripepi, Riccardo Moia, Anna Grazia Recchia, Paola Boggione, Francesca Romana Mauro, Sabrina Bossio, Graziella D'Arrigo, Enrica Antonia Martino, Ernesto Vigna, Francesca Storino, Gilberto Fronza, Francesco Di Raimondo, Davide Rossi, Adalgisa Condoluci, Monica Colombo, Franco Fais, Sonia Fabris, Robin Foa, Giovanna Cutrona, Massimo Gentile, Emili Montserrat, Gianluca Gaidano, Manlio Ferrarini, Antonino Neri
Summary: The study investigated the prognostic value of LDT in CLL patients, revealing that patients with LDT > 12 months had significantly longer TTFT. Combining LDT with other prognostic factors can lead to more accurate risk prediction for CLL patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Fortunato Morabito, Elena Zamagni, Concetta Conticello, Vincenzo Pavone, Salvatore Palmieri, Sara Bringhen, Monica Galli, Silvia Mangiacavalli, Daniele Derudas, Elena Rossi, Roberto Ria, Lucio Catalano, Paola Tacchetti, Giuseppe Mele, Iolanda Donatella Vincelli, Enrica Antonia Martino, Ernesto Vigna, Cirino Botta, Antonella Bruzzese, Anna Mele, Lucia Pantani, Serena Rocchi, Bruno Garibaldi, Nicola Cascavilla, Stelvio Ballanti, Giovanni Tripepi, Ferdinando Frigeri, Antonetta Pia Falcone, Clotilde Cangialosi, Giovanni Reddiconto, Giuliana Farina, Marialucia Barone, Ilaria Rizzello, Pellegrino Musto, Valerio De Stefano, Maurizio Musso, Maria Teresa Petrucci, Massimo Offidani, Antonino Neri, Nicola Di Renzo, Francesco Di Raimondo, Mario Boccadoro, Michele Cavo, Massimo Gentile
Summary: The non-randomized comparison between KRd and EloRd therapies in relapsed/refractory multiple myeloma patients showed that KRd treatment led to a higher probability of achieving a CR+VGPR response, reduced progression or death risk, and had a greater effect on patients achieving CR+VGPR compared to those achieving < VGPR. The overall results suggest potential benefits of KRd therapy over EloRd in clinical practice.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Serena Matis, Martina Rossi, Lorenzo Brondolo, Martina Cardillo, Daniele Reverberi, Rosanna Massara, Monica Colombo, Adalberto Ibatici, Emanuele Angelucci, Tiziana Vaisitti, Silvia Bruno, Sonia Fabris, Antonino Neri, Massimo Gentile, Fortunato Morabito, Giovanna Cutrona, Paola Briata, Roberto Gherzi, Franco Fais
Summary: Long non-coding RNA LINC00152 expression is regulated by immunomodulatory signals in normal B cells, but its role in Chronic Lymphocytic Leukemia (CLL) cells is less effective. Despite variable expression in CLL patients, LINC00152 does not appear to contribute significantly to CLL cell expansion or survival.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Hematology
Domenica Giannandrea, Natalia Platonova, Michela Colombo, Mara Mazzola, Valentina Citro, Raffaella Adami, Filippo Maltoni, Silvia Ancona, Vincenza Dolo, Ilaria Giusti, Andrea Basile, Anna Pistocchi, Laura Cantone, Valentina Bollati, Lavinia Casati, Elisabetta Calzavara, Mauro Turrini, Elena Lesma, Raffaella Chiaramonte
Summary: Multiple myeloma (MM) is an incurable hematologic neoplasm with poor prognosis, largely due to the interaction between MM cells and the bone marrow microenvironment. Researchers have found that MM-derived extracellular vesicles (MM-EV) contain the oncogenic NOTCH receptors, which play a crucial role in promoting the protumorigenic activity of MM-EV. These EV can transfer NOTCH2 between cells and increase NOTCH signaling in target cells, leading to increased angiogenesis and osteoclast differentiation. Targeting the NOTCH pathway may be a promising therapeutic strategy to inhibit the protumorigenic role of EV in MM and other tumors.
Editorial Material
Cell Biology
Michela Colombo, Ruggiero Norfo, Giada Bianchi, Aldo M. Roccaro
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tommaso Laurenzi, Luca Palazzolo, Elisa Taiana, Simona Saporiti, Omar Ben Mariem, Uliano Guerrini, Antonino Neri, Ivano Eberini
Summary: Researchers investigated the stability of NONO and SFPQ dimers, finding that heterodimerization is more favorable than homodimer formation; they also found that the RRM2 subunits of NONO and SFPQ are primarily required for protein-protein interactions with other DBHS protomers; their findings could contribute to the design of small molecules to modulate the activity of these proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Elisa Taiana, Cecilia Bandini, Vanessa Katia Favasuli, Domenica Ronchetti, Ilaria Silvestris, Noemi Puccio, Katia Todoerti, Silvia Erratico, Domenica Giannandrea, Niccolo Bolli, Nicola Amodio, Alessia Ciarrocchi, Raffaella Chiaramonte, Yvan Torrente, Roberto Piva, Antonino Neri
Summary: Long non-coding RNA NEAT1 is deregulated in multiple myeloma patients and its silencing negatively affects MM cell proliferation and viability, indicating a role in DNA damage repair. NEAT1 overexpression provides oncogenic and prosurvival advantages, especially in stressful conditions like nutrient starvation or hypoxia. NEAT1 is involved in various DNA damage repair processes through the regulation of essential PS proteins and the molecular axis of ATM and DNA-PK kinase proteins.
Article
Biochemistry & Molecular Biology
Antonio Matera, Alessio Marella, Akihiro Maeda, Matteo C. Da Via, Francesca Lazzaroni, Sonia Fabris, Stefania Pioggia, Laura Porretti, Federico Colombo, Federica Torricelli, Antonino Neri, Elisa Taiana, Giuseppina Fabbiano, Valentina Traini, Elisa Genuardi, Daniela Drandi, Niccolo Bolli, Marta Lionetti
Summary: Multiple myeloma (MM) has a heterogeneous genetic background, making it difficult to track. However, each MM patient's malignant plasma cells share unique V(D)J rearranged sequences, which can serve as ideal disease biomarkers. By using single-cell RNA sequencing, the dominant clonotype in each sample can be easily identified, and clonal productive rearrangements can be accurately detected. This method may be used to track rare clonal cells and lay the foundation for functional single-cell analysis of minimal residual disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Abdullah O. Khan, Antonio Rodriguez-Romera, Jasmeet S. Reyat, Aude-Anais Olijnik, Michela Colombo, Guanlin Wang, Wei Xiong Wen, Nikolaos Sousos, Lauren C. Murphy, Beata Grygielska, Gina Perrella, Christopher B. Mahony, Rebecca E. Ling, Natalina E. Elliott, Christina Simoglou Karali, Andrew P. Stone, Samuel Kemble, Emily A. Cutler, Adele K. Fielding, Adam P. Croft, David Bassett, Gowsihan Poologasundarampillai, Anindita Roy, Sarah Gooding, Julie Rayes, Kellie R. Machlus, Bethan Psaila
Summary: This study presents a human bone marrow organoid that can support the growth and survival of primary cells from patients with myeloid and lymphoid blood cancers. This organoid model allows for mechanistic studies of blood cancers within their microenvironment and serves as an ex vivo tool for prioritizing new therapeutics.
Article
Oncology
Domenica Ronchetti, Vanessa Katia Favasuli, Ilaria Silvestris, Katia Todoerti, Federica Torricelli, Niccolo Bolli, Alessia Ciarrocchi, Elisa Taiana, Antonino Neri
Summary: NONO is overexpressed in MM and higher expression levels are significant independent prognostic markers of worse clinical outcome. NONO deregulation may play a pathogenetic role in MM by affecting cell cycle, DNA repair mechanisms, translation, and glucose metabolism.