Review
Medicine, General & Internal
Daniela Drandi, Philippe Decruyenaere, Martina Ferrante, Fritz Offner, Jo Vandesompele, Simone Ferrero
Summary: This review aims to provide a comprehensive overview of molecular biomarkers in Waldenstrom Macroglobulinemia (WM) and IgM gammopathies, and explore their potential applications in precision medicine.
Article
Biochemistry & Molecular Biology
Shahrzad Jalali, Jie Shi, Nagib Ahsan, LindaE Wellik, MaKayla Serres, Alex Buko, Jonas Paludo, HyoJin Kim, XinYi Tang, Zhi-Zhang Yang, AnneJ Novak, RobertA Kyle, StephenM Ansell
Summary: This study identified crucial lipid metabolism changes in the progression from IgM-MGUS to WM through molecular analysis of patient serum samples. The data suggest that reduced levels of lipid metabolites in WM patients' serum are associated with increased lipid peroxidation, and downregulation of 15-LOX increases the survival of WM cells. These findings are significant in identifying disease progression biomarkers and designing targeted therapeutic interventions.
Article
Genetics & Heredity
Yuan Xiang, Shi-Qiang Fang, Yi-Wen Liu, Hui Wang, Zhong-Xin Lu
Summary: Waldenstrom Macroglobulinemia (WM) is a rare blood cancer characterized by abnormal increase of monoclonal IgM in the blood. This case report is the first to document a male patient with WM who experienced a mutation from lgM to abnormal lgG after 6 years of treatment.
FRONTIERS IN GENETICS
(2023)
Article
Multidisciplinary Sciences
Jun Hee Lim, James Q. Wang, Fiona Webb, Kartik Saxena, Daniel Enosi Tuipulotu, Abhimanu Pandey, Si Ming Man, Dipti Talaulikar
Summary: Waldenstrom macroglobulinemia (WM) is characterized by the presence of a specific mutation in both malignant plasma cells (PCs) and lymphoplasmacytic cells (LPCs), and the expression of the same auto-reactive IgHV sequences in both cell types. Malignant PCs are primarily responsible for the secretion of IgM, and targeting these cells may be beneficial in the treatment of WM.
Article
Oncology
Mona Karbalivand, Luciana L. Almada, Stephen M. Ansell, Martin E. Fernandez-Zapico, Sherine F. Elsawa
Summary: This study identified MLL1 histone methyltransferase and its partner Menin as upregulated factors in Waldenstrom macroglobulinemia (WM) patients. Inhibition of MLL1 function or disruption of the Menin-MLL1 complex resulted in a significant reduction in IgM levels. These findings suggest that MLL1 could be a novel therapeutic target for WM.
Article
Oncology
Jorge J. Castillo, John N. Allan, Tanya Siddiqi, Ranjana H. Advani, Kirsten Meid, Carly Leventoff, Timothy P. White, Catherine A. Flynn, Shayna Sarosiek, Andrew R. Branagan, Maria G. Demos, Maria L. Guerrera, Amanda Kofides, Xia Liu, Manit Munshi, Nicholas Tsakmaklis, Lian Xu, Guang Yang, Christopher J. Patterson, Zachary R. Hunter, Matthew S. Davids, Richard R. Furman, Steven P. Treon
Summary: Venetoclax demonstrates safety and efficacy in previously treated WM patients, including those who previously received BTKis. CXCR4 mutation status does not affect treatment response.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Oncology
Morie A. Gertz
Summary: With the introduction of new effective therapeutic options, a structured approach to managing macroglobulinemia is needed. The authors conducted a review of treatment trials and provided therapeutic options based on the best available evidence.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ava J. Boutilier, Lina Huang, Sherine F. Elsawa
Summary: This review explores avenues of tumor progression and targeted drug therapy that have been investigated in Waldenstrom macroglobulinemia and related B-cell lymphomas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Maaya Awata-Shiraiwa, Akihiko Yokohama, Yukihiro Kanai, Nanami Gotoh, Tetsuhiro Kasamatsu, Hiroshi Handa, Takayuki Saitoh, Hirokazu Murakami, Junko Hirato, Hayato Ikota, Norifumi Tsukamoto
Summary: Using targeted next-generation sequencing (NGS), this study found no significant genetic differences between Waldenstrom macroglobulinemia (WM) and non-IgM-type lymphoplasmacytic lymphoma (LPL). These findings suggest genetic similarities between these two subsets of LPL.
ACTA HAEMATOLOGICA
(2023)
Review
Hematology
Simone A. Brysland, M. Gohar Maqbool, Dipti Talaulikar, Elizabeth E. Gardiner
Summary: Waldenstrom macroglobulinemia (WM) is a rare and incurable B cell lymphoma that often leads to symptoms such as anemia, bleeding, and neurological symptoms. The bleeding phenotype in WM is complex and may involve factors such as platelet dysfunction, hyperviscosity, abnormal hematopoiesis, cryoglobulinemia, and amyloidosis. Understanding the pathophysiological mechanisms behind bleeding is important for clinical decision-making and treatment management.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Danka Cholujova, Gabor Beke, Zachary R. Hunter, Teru Hideshima, Ludmila Flores, Tatiana Zeleznikova, Denisa Harrachova, Lubos Klucar, Merav Leiba, Lubos Drgona, Steven P. Treon, Efstathios Kastritis, David M. Dorfman, Kenneth C. Anderson, Jana Jakubikova
Summary: By using mass cytometry, this study characterized the immunophenotypic changes in Waldenstrom macroglobulinemia (WM) and revealed the modulation of immune cells by immune checkpoints. It was found that the response to treatment strategies in WM can be monitored by observing the changes in immune cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Hematology
Ramon Garcia-Sanz, Irene Dogliotti, Gian Maria Zaccaria, Enrique Maria Ocio, Araceli Rubio, Ilda Murillo, Fernando Escalante, Carmen Aguilera, Aranzazu Garcia-Mateo, Alfonso Garcia de Coca, Roberto Hernandez, Julio Davila, Noemi Puig, Maria Garcia-Alvarez, Maria del Carmen Chillon, Miguel Alcoceba, Alejandro Medina, Veronica Gonzalez de la Calle, Maria Eugenia Sarasquete, Marcos Gonzalez, Norma Carmen Gutierrez, Cristina Jimenez
Summary: The presence of del6q in IgM gammopathy is associated with symptomatic disease, need for treatment and poorer clinical outcomes.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Morie A. Gertz
Summary: WM is a lymphoma with IgM monoclonal protein, diagnosed by presence of clonal lymphoplasmacytic cells and MYD88 gene mutation. Predictive characteristics for outcomes include age, hemoglobin level, platelet count, beta(2) microglobulin, LDH, and monoclonal IgM concentrations. Treatment options include rituximab and bendamustine as preferred induction, with various other agents showing activity in relapsed cases of refractory disease.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Review
Pharmacology & Pharmacy
Shayna Sarosiek, Steven P. Treon, Jorge J. Castillo
Summary: The treatment of WM can lead to a variety of adverse events, including myeloid neoplasms, IgM flares, infusion reactions, neuropathy, bleeding, and cardiac arrhythmias. Clinicians can use dose reductions, lower cycles, and changes in route of administration to manage and minimize toxicity while future research focuses on improving patient safety.
EXPERT OPINION ON DRUG SAFETY
(2021)
Review
Oncology
Shayna Sarosiek, Steven P. Treon, Jorge J. Castillo
Summary: There are multiple treatment options available for Waldenstrom macroglobulinemia patients, including chemotherapy, monoclonal antibodies, proteasome inhibitors, and covalent Bruton tyrosine kinase (BTK) inhibitors. Treatment decisions should be personalized based on the patient's clinical presentation, genetic profile, and treatment preferences. While ibrutinib monotherapy is favored in certain genetic subtypes, other options like chemoimmunotherapy or proteasome inhibitor-based regimens should also be considered.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2021)
Editorial Material
Hematology
Attilio Orazi, Robert P. Hasserjian, Mario Cazzola, Hartmut Dohner, Ayalew Tefferi, Daniel A. Arber
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Hideki Makishima, Ryunosuke Saiki, Yasuhito Nannya, Sophia Korotev, Carmelo Gurnari, June Takeda, Yukihide Momozawa, Steve Best, Pramila Krishnamurthy, Tetsuichi Yoshizato, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Nobuyuki Kakiuchi, Makoto Onizuka, Kenichi Chiba, Hiroko Tanaka, Ayana Kon, Yotaro Ochi, Masahiro M. Nakagawa, Rurika Okuda, Takuto Mori, Akinori Yoda, Hidehiro Itonaga, Yasushi Miyazaki, Masashi Sanada, Takayuki Ishikawa, Shigeru Chiba, Hisashi Tsurumi, Senji Kasahara, Carsten Mueller-Tidow, Akifumi Takaori-Kondo, Kazuma Ohyashiki, Toru Kiguchi, Fumihiko Matsuda, Joop H. Jansen, Chantana Polprasert, Piers Blombery, Yoichiro Kamatani, Sator Miyano, Luca Malcovati, Torsten Haferlach, Michiaki Kubo, Mario Cazzola, Austin G. Kulasekararaj, Lucy A. Godley, Jaroslaw P. Maclejewski, Seishi Ogawa
Summary: DDX41 gene mutations play an important role in late-onset myeloid neoplasms, but many crucial features of DDX41-mutated neoplasms still need to be elucidated. This study comprehensively characterized DDX41-mutated neoplasms and found that DDX41 risk variants accounted for 80% of known genetic predispositions to myeloid neoplasms in adults. Additionally, DDX41 risk alleles were significantly enriched in Japanese cases and more prominent in males compared to females.
Letter
Oncology
Riccardo Moia, Riccardo Dondolin, Maria Stefania De Propris, Donatella Talotta, Samir Mouhssine, Francesca Perutelli, Gianluigi Reda, Veronica Mattiello, Gian Matteo Rigolin, Marina Motta, Jacopo Olivieri, Renato Fanin, Omar Perbellini, Isacco Ferrarini, Francesca Romana Mauro, Ilaria Del Giudice, Luca Laurenti, Annamaria Tomasso, Massimo Gentile, Anna Maria Frustaci, Alessandra Tedeschi, Alessandro Gozzetti, Caterina Stelitano, Carlo Visco, Carol Moreno, Francesco Forconi, Roberto Marasca, Marta Coscia, Davide Rossi, Robin Foa, Gianluca Gaidano
HEMATOLOGICAL ONCOLOGY
(2023)
Letter
Hematology
Shai Levi, Yotam Bronstein, Neta Goldschmidt, Fortunato Morabito, Tomer Ziv-Baran, Giovanni Del Poeta, Osnat Bairey, Maria Ilaria Del Principe, Riva Fineman, Francesca Romana Mauro, Odit Gutwein, Gianluigi Reda, Rosa Ruchlemer, Paolo Sportoletti, Luca Laurenti, Lev Shvidel, Marta Coscia, Tamar Tadmor, Marzia Varettoni, Ariel Aviv, Roberta Murru, Andrei Braester, Annalisa Chiarenza, Andrea Visentin, Daniela Pietrasanta, Giacomo Loseto, Antonella Zucchetto, Riccardo Bomben, Jacopo Olivieri, Antonio Neri, Davide Rossi, Gianluca Gaidano, Livio Trentin, Robin Foa, Antonio Cuneo, Chava Perry, Valter Gattei, Massimo Gentile, Yair Herishanu
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Christian Pecquet, Nicolas Papadopoulos, Thomas Balligand, Ilyas Chachoua, Amandine Tisserand, Audrey Nedelec, Didier Vertommen, Anita Roy, Caroline Marty, Harini Nivarthi, Mira El-Khoury, Eva Hug, Andrea Majoros, Erica Xu, Oleh Zagrijtschuk, Tudor E. Fertig, Daciana S. Marta, Heinz Gisslinger, Bettina Gisslinger, Martin Schalling, Ilaria Casetti, Elisa Rumi, Daniela Pietra, Chiara Cavalloni, Luca Arcaini, Mario Cazzola, Norio Komatsu, Yoshihiko Kihara, Yoshitaka Sunami, Yoko Edahiro, Marito Araki, Roman Lesyk, Veronika Buxhofer-Ausch, Sonja Heibl, Florence Pasquier, Violaine Havelange, Isabell Plo, William Vainchenker, Robert Kralovics, Stefan N. Constantinescu
Summary: Mutant CALR proteins bind to and activate the TpoR in cells, driving the development of myeloproliferative neoplasms. These mutant CALR proteins can be found in patient plasma complexed with sTFR1, which increases their stability. They can specifically interact with TpoR on target cells and promote thrombopoietin-independent colony formation.
Letter
Hematology
Fortunato Morabito, Giovanni Tripepi, Francesca Romana Mauro, Luca Laurenti, Gianluigi Reda, Riccardo Moia, Adalgisa Condoluci, Iolanda Vincelli, Annalisa Chiarenza, Ernesto Vigna, Enrica Antonia Martino, Antonella Bruzzese, Sabrina Mezzatesta, Roberta Laureana, Giovanna Cutrona, Francesco Di Raimondo, Gilberto Fronza, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Jacopo Olivieri, Francesco Zaja, Davide Rossi, Gianluca Gaidano, Maria Ilaria Del Principe, Fiorella Ilariucci, Giovanni Del Poeta, Manlio Ferrarini, Antonino Neri, Valter Gattei, Massimo Gentile
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Editorial Material
Hematology
Mario Cazzola
Review
Oncology
Emanuele Zucca, Davide Rossi, Francesco Bertoni
Summary: The three main types of marginal zone lymphoma (MZL) are extranodal MZL of mucosa-associated lymphoid tissue, splenic MZL, and nodal MZL. They share certain karyotype lesions and alterations in the NFkB pathway. However, they differ in the presence of recurrent translocations, mutations affecting the Notch signaling pathway, the transcription factors KLF2 or PTPRD. This review summarizes recent advances in understanding the epidemiology, genetics, and biology of MZLs, as well as the standard management principles.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Simona De Gregori, Eleonora Gelli, Mara Capone, Giulia Gambini, Elisa Roncoroni, Marianna Rossi, Claudia Patricia Tobar Cabrera, Gianluca Martini, Ludovica Calabretta, Luca Arcaini, Riccardo Albertini, Patrizia Zappasodi
Summary: The combination of hypomethylating agents (HMA) azacytidine or decitabine with venetoclax (VEN) has been approved by the FDA for the treatment of acute myeloid leukemia (AML) patients aged over 75 years and those unsuitable for intensive chemotherapy. To prevent fungal infection during the early phase of treatment, posaconazole (PCZ) is commonly administered as primary prophylaxis. 165 plasma samples from 11 elderly AML patients receiving combined treatment with HMA, VEN, and PCZ were analyzed to determine the serum levels of venetoclax and the need for therapeutic drug monitoring due to high inter-individual variability in pharmacokinetics.
Article
Microbiology
Valentina Zuccaro, Greta Petazzoni, Irene Mileto, Marta Corbella, Erika Asperges, Paolo Sacchi, Sara Rattotti, Marzia Varettoni, Irene Defrancesco, Patrizia Cambieri, Fausto Baldanti, Luca Arcaini, Raffaele Bruno
Summary: Several studies have shown a strong connection between gut microbiota and the response to immunotherapy in tumor patients, suggesting that gut microbiota can serve as a biomarker for response. This study aimed to compare the gut microbiota diversity in chronic lymphocytic leukemia patients treated with B-cell receptor inhibitors for at least 12 months. The findings revealed differences in bacterial distribution between different response groups.
Article
Hematology
Elaine Y. L. Chung, Giulio Sartori, Maurilio Ponzoni, Luciano Cascione, Valdemar Priebe, Zijun Y. Xu-Monette, Xiaosheng Fang, Mingzhi Zhang, Carlo Visco, Alexandar Tzankov, Andrea Rinaldi, Jacopo Sgrignani, Emanuele Zucca, Davide Rossi, Andrea Cavalli, Giorgio Inghirami, David W. W. Scott, Ken H. H. Young, Francesco Bertoni
Summary: The role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL was studied in cellular models and clinical specimens. It was found that p-ETS1 was detected in activated B cell-like DLBCL (ABC), not in germinal centre B-cell-like DLBCL (GCB), and its inhibition could benefit lymphoma patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Riccardo Moia, Lodovico di Terzi Bergamo, Donatella Talotta, Riccardo Bomben, Gabriela Forestieri, Valeria Spina, Alessio Bruscaggin, Chiara Cosentino, Mohammad Almasri, Riccardo Dondolin, Tamara Bittolo, Antonella Zucchetto, Stefano Baldoni, Ilaria Del Giudice, Francesca Romana Mauro, Rossana Maffei, Annalisa Chiarenza, Agostino Tafuri, Roberta Laureana, Maria Ilaria Del Principe, Francesco Zaja, Giovanni D'Arena, Jacopo Olivieri, Silvia Rasi, Abdurraouf Mahmoud, Wael Al Essa, Bassel Awikeh, Sreekar Kogila, Matteo Bellia, Samir Mouhssine, Paolo Sportoletti, Roberto Marasca, Lydia Scarfo, Paolo Ghia, Valter Gattei, Robin Foa, Davide Rossi, Gianluca Gaidano
Summary: XPO1 mutations in CLL were found to be associated with increased binding sites for transcription factors regulated by pathways emanating from the B-cell receptor. These mutations also resulted in transcriptomic features associated with BCR and cytokine signalling. In a study of 957 early-stage CLL cases, XPO1 mutations were identified as a novel predictor of shorter time to first treatment, independent of immunoglobulin status and early-stage prognostic models.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Oncology
Ilaria Romano, Adalgisa Condoluci, Davide Rossi
Summary: Richter's transformation is a rare condition where aggressive lymphoma develops from underlying chronic lymphocytic leukemia/small lymphocytic lymphoma. Traditional treatment options have limited success, but novel targeted therapies show promising results. Noncovalent Bruton tyrosine kinase inhibitors, T-cell-engaging bispecific antibodies, chimeric antigen receptor T-cells, and conjugated monoclonal antibodies may improve treatment outcomes.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Correction
Hematology
A. Larocca, F. Bonello, G. Gaidano
Article
Oncology
Carla Casulo, Armando Santoro, Guillaume Cartron, Kiyoshi Ando, Javier Munoz, Steven Le Gouill, Koji Izutsu, Simon Rule, Pieternella Lugtenburg, Jia Ruan, Luca Arcaini, Marie-Laure Casadebaig, Brian Fox, Nurgul Kilavuz, Nils Rettby, Justine Dell'Aringa, Lilia Taningco, Richard Delarue, Myron Czuczman, Thomas Witzig
Summary: The immune checkpoint inhibitor durvalumab shows potential as a strategy for enhancing immune responses and improving standard therapies in patients with hematologic malignancies. This study evaluated the safety and efficacy of durvalumab in combination with standard-of-care therapies for lymphoma or chronic lymphocytic leukemia (CLL) and found limited benefits of durvalumab monotherapy or combination therapy.
