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)
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.
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)
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)
Review
Pharmacology & Pharmacy
Md Sahab Uddin, Md Tanvir Kabir, Abdullah Al Mamun, Md Shahid Sarwar, Fatema Nasrin, Talha Bin Emran, Ibtesam S. Alanazi, Abdur Rauf, Ghadeer M. Albadrani, Amany A. Sayed, Shaker A. Mousa, Mohamed M. Abdel-Daim
Summary: NF-κB is a critical transcription factor that is abnormally activated in several cancers, particularly in glioblastoma multiforme (GBM). Despite the use of various treatment modalities for GBM, the survival rate of patients remains low, highlighting the need for new therapeutic approaches.
FRONTIERS IN PHARMACOLOGY
(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)
Review
Hematology
Jorge J. Castillo, Christian Buske, Judith Trotman, Shayna Sarosiek, Steven P. Treon
Summary: BTK inhibitors play a crucial role in the treatment of Waldenstrom macroglobulinemia, being the only FDA-approved agents for these patients. However, there are still unmet needs with BTK inhibitor therapy, such as indefinite duration therapy, high cost, scarcity of complete responses, and lower response rates in patients with CXCR4 mutations. This review focuses on the data supporting the use of covalent BTK inhibitors, management issues, clinical trials with covalent BTK inhibitor combination regimens, and upcoming non-covalent BTK inhibitors.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Hao Sun, Teng Fang, Tingyu Wang, Zhen Yu, Lixin Gong, Xiaojing Wei, Huijun Wang, Yi He, Lanting Liu, Yuting Yan, Weiwei Sui, Yan Xu, Shuhua Yi, Lugui Qiu, Mu Hao
Summary: By using single-cell RNA sequencing, this study revealed the cellular heterogeneity in the bone marrow of Waldenstrom macroglobulinemia (WM) and the co-evolution between malignant cells and immune cells. Two novel subpopulations of malignant cells were identified, and the potential molecular mechanisms of immune cell dysfunction were investigated.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Stephan J. Matissek, Weiguo Han, Mona Karbalivand, Mohamed Sayed, Brendan M. Reilly, Shayna Mallat, Shimaa M. Ghazal, Manit Munshi, Guang Yang, Steven P. Treon, Sarah R. Walker, Sherine F. Elsawa
Summary: The study demonstrates that BET inhibitors are effective in reducing the growth of WM cells, especially when used in combination with other drugs. This provides a new approach for developing novel therapies for WM.
Article
Hematology
Cecile Tomowiak, Stephanie Poulain, Charles Herbaux, Aurore Perrot, Beatrice Mahe, Pierre Morel, Therese Aurran, Olivier Tournilhac, Stephane Lepretre, Souad Assaad, Bruno Villemagne, Olivier Casasnovas, Delphine Nollet, Damien Roos-Weil, Sylvie Chevret, Veronique Leblond
Summary: The combination of idelalisib + obinutuzumab was effective in treating R/R WM, with high overall response rate and major response rate. Genetic factors, specifically CXCR4 genotypes, did not significantly impact treatment outcomes, but TP53 mutations were associated with poorer survival. However, some patients discontinued the study due to side effects.
Letter
Oncology
Eugenio Morelli, Zachary R. Hunter, Mariateresa Fulciniti, Annamaria Gulla, Ida Daniela Perrotta, Valeria Zuccala, Cinzia Federico, Giada Juli, Martina Manzoni, Domenica Ronchetti, Enrica Romeo, Maria Eugenia Gallo Cantafio, Debora Soncini, Lorenza Maltese, Marco Rossi, Aldo M. Roccaro, Michele Cea, Pierfrancesco Tassone, Antonino Neri, Steven C. Treon, Nikhil C. Munshi, Giuseppe Viglietto, Nicola Amodio
Summary: Activation of G protein-coupled estrogen receptor 1 (GPER1) in tumor cells from Waldenstrom Macroglobulinemia (WM) patients leads to cell cycle arrest and apoptosis, even in the protective bone marrow environment, providing a novel therapeutic target for the treatment of WM.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
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)
Editorial Material
Genetics & Heredity
Gilles Salbert, Aurelien A. Serandour, Bart Staels, Philippe Lefebvre, Jerome Eeckhoute
Article
Hematology
Cirino Botta, Catarina Maia, Juan-Jose Garces, Rosalinda Termini, Cristina Perez, Irene Manrique, Leire Burgos, Aintzane Zabaleta, Diego Alignani, Sarai Sarvide, Juana Merino, Noemi Puig, Maria-Teresa Cedena, Marco Rossi, Pierfrancesco Tassone, Massimo Gentile, Pierpaolo Correale, Ivan Borrello, Evangelos Terpos, Tomas Jelinek, Artur Paiva, Aldo Roccaro, Hartmut Goldschmidt, Herve Avet-Loiseau, Laura Rosinol, Maria-Victoria Mateos, Joaquin Martinez-Lopez, Juan-Jose Lahuerta, Joan Blade, Jesus F. San-Miguel, Bruno Paiva
Summary: Large-scale immune monitoring is increasingly used in clinical trials, but manual interpretation of multidimensional data poses challenges. FlowCT is a semi-automated workspace that can analyze large datasets, including preprocessing, normalization, dimensionality reduction, clustering, and predictive modeling tools.
Article
Multidisciplinary Sciences
Jing Ni, Sheheryar Kabraji, Shaozhen Xie, Yanzhi Wang, Peichen Pan, Xiaofang He, Zongming Liu, Jose Palbo Leone, Henry W. Long, Myles A. Brown, Eric P. Winer, A. R. Dillon, Nancy U. Lin, Jean J. Zhao
Summary: HER2-positive breast cancer often develops brain metastases (BCBMs) that are difficult to treat. The loss of p16(INK4A) in BCBMs from HER2-positive breast tumors results in resistance to the HER2 inhibitor Tucatinib, but this sensitivity can be restored by CDK4/6 inhibition. This study reveals the deficiency of p16(INK4A) in HER2-positive BCBMs and suggests a biomarker-driven clinical trial using combined CDK4/6 and HER2-targeted agents for treating HER2-positive BCBM patients.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Cell Biology
Jerome Eeckhoute
Article
Biochemical Research Methods
Allen W. Lynch, Christina Theodoris, Henry Long, Myles Brown, X. Shirley Liu, Clifford A. Meyer
Summary: MIRA is a comprehensive methodology that compares gene expression and chromatin accessibility in single cells to infer regulatory mechanisms driving cell fate transitions. It models cell states and regulatory potential of gene loci to represent cell states in an efficient and interpretable latent space, and reveals the variable influence of local accessibility on transcription at different gene loci.
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.
Meeting Abstract
Hematology
Andrew R. Branagan, Matthew M. Lei, Clifton C. Mo, Andrew J. Yee, Elizabeth K. O'Donnell, Jorge J. Castillo, Omar Nadeem, Noopur Raje, Steven P. Treon, Paul G. Richardson, Rie Nakamoto-Matsubara, Kirsten Meid, Zachary S. Bernstein, Rebecca T. Lyons, Rakesh Verma, Zachary R. Hunter, Maria Luisa Guerrera, Catherine A. Flynn, Jill N. Burke, Cynthia C. Harrington, Emerentia Agyemang, Marilyn T. Gammon, Kathleen J. Lively, Lisette Packer, Nora K. Horick, Shayna Sarosiek
Meeting Abstract
Hematology
Maria Luisa Guerrera, Xia Liu, Eugenio Morelli, Kris Richardson, Nickolas Tsakmaklis, Amanda Kofides, Manit Munshi, Shirong Liu, Guang Yang, Christopher J. Patterson, Jorge J. Castillo, Shayna Sarosiek, Catherine A. Flynn, Kirsten Meid, Joshua Gustine, Andrew R. Branagan, Alessandra Trojani, Alessandra Tedeschi, Roberto Cairoli, Tomasz Sewastianik, Ruben D. Carrasco, Kenneth C. Anderson, Nikhil C. Munshi, Steven P. Treon, Zachary R. Hunter
Meeting Abstract
Hematology
Kris Richardson, Jorge J. Castillo, Shayna Sarosiek, Andrew R. Branagan, Catherine A. Flynn, Kirsten Meid, Carly Leventoff, Timothy P. White, Megan Little, Joshua Gustine, Xia Liu, Amanda Kofides, Shirong Liu, Alexa Canning, Julie Wolf, Katherine Kacena, Christopher J. Patterson, Maria Luisa Guerrera, Nickolas Tsakmaklis, Steven P. Treon, Zachary R. Hunter
Meeting Abstract
Hematology
Jorge J. Castillo, Shayna Sarosiek, Andrew R. Branagan, David J. Sermer, Catherine A. Flynn, Carly Leventoff, Megan Little, Timothy P. White, Kirsten Meid, Alexa Canning, Maria Luisa Guerrera, Amanda Kofides, Xia Liu, Manit Munshi, Nicholas Tsakmaklis, Christopher J. Patterson, Zachary R. Hunter, Steven P. Treon
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, Marzia Varettoni, Cristina Jimenez, Simone Ferrero, Stephanie Poulain, Jesus F. San-Miguel, Maria L. Guerrera, Daniela Drandi, Tina Bagratuni, Mary McMaster, Aldo M. Roccaro, Damien Roos-Weil, Merav Leiba, Yong Li, Luigi Qiu, Jian Hou, C. Fernandez De Larrea, Jorge J. Castillo, M. Dimopoulos, R. G. Owen, S. P. Treon, Z. R. Hunter
Summary: In addition to the MYD88L265P mutation, there is extensive information on the molecular mechanisms in Waldenstrom's Macroglobulinemia and its potential utility in the diagnosis and treatment tailoring. However, there are currently no consensus recommendations available. The key recommendations from the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) Consensus Panel 3 (CP3) focus on the necessity of molecular studies for proper diagnosis and monitoring.
SEMINARS IN HEMATOLOGY
(2023)
Editorial Material
Hematology
Antonio Sacco, Aldo M. Roccaro
Summary: In this study, it is shown that cyclin-dependent kinase-7 (CDK7) affects the oncogenic programming of multiple myeloma (MM) cells through modulation of MYC and E2F transcription factors. The authors demonstrate that inhibiting CDK7 counteracts E2F activity, resulting in reduced CDKs-retinoblastoma (Rb) axis and inhibition of MYC-regulated metabolic signatures. Therefore, CDK7 inhibition is a promising therapeutic target for MM.
Article
Multidisciplinary Sciences
Allen W. Lynch, Myles Brown, Clifford A. Meyer
Summary: In this study, the authors propose a method that can effectively analyze batch-confounded chromatin and gene expression states by separating technical and biological effects. The cell state atlases constructed through single-cell RNA-seq and ATAC-seq analysis are powerful tools for studying perturbation effects on complex cell systems. Comparing these atlases can provide new insights into cell state and trajectory alterations.
NATURE COMMUNICATIONS
(2023)