Article
Oncology
Nitin Jain, Philip Thompson, Jan Burger, Alessandra Ferrajoli, Koichi Takahashi, Zeev Estrov, Gautam Borthakur, Prithviraj Bose, Tapan Kadia, Naveen Pemmaraju, Koji Sasaki, Marina Konopleva, Elias Jabbour, Naveen Garg, Xuemei Wang, Rashmi Kanagal-Shamanna, Keyur Patel, Wei Wang, Jeffrey Jorgensen, Sa Wang, Wanda Lopez, Ana Ayala, William Plunkett, Varsha Gandhi, Hagop Kantarjian, Susan O'Brien, Michael Keating, William G. Wierda
Summary: The iFCG regimen with only 3 cycles of chemotherapy is an effective, time-limited regimen for patients with CLL with mutated IGHV and without del(17p)/TP53 mutation. The treatment resulted in high rates of complete remission and undetectable measurable residual disease in the marrow, with excellent 3-year progression-free and overall survival rates.
Article
Medicine, Research & Experimental
Chao Guo, Ya-yue Gao, Qian-qian Ju, Chun-xia Zhang, Ming Gong, Zhen-ling Li
Summary: The study identified co-expression modules and hub genes correlating with IGHV mutation status in CLL patients. These genes are associated with important signaling pathways and have prognostic value for CLL patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Hematology
Nyla A. Heerema, Natarajan Muthusamy, Qiuhong Zhao, Amy S. Ruppert, Heather Breidenbach, Leslie A. Andritsos, Michael R. Grever, Kami J. Maddocks, Jennifer Woyach, Farrukh Awan, Meixiao Long, Amber Gordon, Caitlin Coombes, John C. Byrd
Summary: Mutations in the IGH variable region are associated with a favorable prognosis in patients with chronic lymphocytic leukemia, while cytogenetic complexity and translocations are linked to an unfavorable prognosis. The presence of a translocation in IGHV-mutated patients appears to negate the improved prognosis of mutated IGHV.
Article
Oncology
Uffe Klausen, Jacob Handlos Grauslund, Nicolai Gronne Dahlager Jorgensen, Shamaila Munir Ahmad, Merete Jonassen, Stine Emilie Weis-Banke, Evelina Martinenaite, Lone Bredo Pedersen, Thomas Landkildehus Lisle, Anne Ortved Gang, Lisbeth Enggaard, Morten Hansen, Morten Orebo Holmstrom, Ozcan Met, Inge Marie Svane, Carsten Utoft Niemann, Lars Moller Pedersen, Mads Hald Andersen
Summary: In the study, CLL patients with unmutated IgHV were treated with a therapeutic cancer vaccine containing peptides derived from PD-L1 and PD-L2. One patient achieved complete normalization of peripheral lymphocyte count during a follow-up of 15 months, while most patients remained stable. The vaccine showed good immunogenicity and tolerability, but as a monotherapy, it may not be sufficient and should be tested in combination with other treatments.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Alexia Suarez-Cabrera, Dolly Viviana Fiallo-Suarez, Ruth Stuckey, Marta Luna Uroz-De la Iglesia, Yanira Florido, Angelina Lemes-Castellano, Miguel Angel Perera-Alvarez, Hugo Luzardo-Henriquez, Haridian De la Nuez, Paula Fernandez-Caldas, Silvia De la Iglesia, Maria Teresa Gomez-Casares, Cristina Bilbao-Sieyro
Summary: This study examined molecular biomarkers in 217 CLL patients and found that unmutated IGHV was associated with shorter overall survival and time to first treatment. Lymphocyte count was not significant for time to first treatment in early-stage patients.
Article
Cell Biology
Dipnarine Maharaj, Gayathri Srinivasan, Maria M. Abreu, Meng-Wei Ko, Anahid Jewett, Jacqueline Gouvea
Summary: Clinical study demonstrates that combining low dose recombinant human IL-2 and low dose targeted therapy can achieve cytogenetic and molecular remission with minimal adverse events in patients with chronic lymphocytic leukemia (CLL).
Article
Immunology
Gema Perez-Chacon, Juan M. Zapata
Summary: Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) is a heterogeneous disease with at least two subtypes, characterized by specific IGHV gene subgroup usage and the existence of stereotyped B-cell receptors. The study on Traf2DN/BCL2-tg(+/+) mice shows remarkable similarities with human CLL/SLL, highlighting the importance of antigen exposure in malignant transformation and clone expansion.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Osvaldo D. Rivera, Michael J. Mallory, Mathieu Quesnel-ValliIres, Rakesh Chatrikhi, David C. Schultz, Martin Carroll, Yoseph Barash, Sara Cherry, Kristen W. Lynch
Summary: In acute myeloid leukemia, alternative splicing events can alter the expression of a subset of genes independently of known somatic mutations. Furthermore, the reduced functional EZH2 in some patients is not solely caused by somatic mutations, indicating a role of aberrant splicing in gene dysregulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Jayalakshmi Balakrishna, Neil Basumallik, Robert Matulonis, Drake Scott, Dalia Salem, Gregory Jasper, Adrian Wiestner, Maryalice Stetler-Stevenson, Gerald Marti, Clare Sun, Constance M. Yuan
Summary: This study demonstrates the prognostic utility of antigen quantitation in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and monoclonal B-cell lymphocytosis (MBL), and finds that different protein expressions are associated with immunoglobulin status, cytogenetic abnormalities, and time to first treatment.
LEUKEMIA & LYMPHOMA
(2021)
Review
Oncology
Sagarajit Mohanty, Michael Heuser
Summary: Acute myeloid leukemia is a biologically diverse blood cancer with variable prognosis, and comprehensive sequencing and mouse models play crucial roles in understanding the genetic mechanisms and drug targets in AML. This review focuses on the leukemogenic function of mutations in seven functional gene groups using evidence from mouse models, providing insights into the cooperative mutations in AML development and their correlation with prognosis.
Article
Oncology
Stefano Baldoni, Beatrice Del Papa, Filomena De Falco, Erica Dorillo, Carlo Sorrentino, Chiara Rompietti, Francesco Maria Adamo, Manuel Nogarotto, Debora Cecchini, Elena Mondani, Estevao Carlos Silva Barcelos, Lorenzo Moretti, Maria Grazia Mameli, Bianca Fabi, Daniele Sorcini, Arianna Stella, Raffaella Giancola, Francesco Guardalupi, Francesca Ulbar, Sara Plebani, Valerio Guarente, Emanuela Rosati, Marta Di Nicola, Michele Marchioni, Mauro Di Ianni, Paolo Sportoletti
Summary: This study found that NOTCH1 activation is a negative prognostic factor in chronic lymphocytic leukemia (CLL) patients, significantly reducing Time To First Treatment (TTFT) regardless of NOTCH1 and IGHV mutation status. Activation of NOTCH2 and expression of JAGGED1 also influence clinical outcomes in this group, highlighting the need for further dedicated studies to refine CLL risk stratification using different components of the NOTCH network.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Matthew Kaufman, Xiao-Jie Yan, Wentian Li, Emanuela M. Ghia, Anton W. Langerak, Laura Z. Rassenti, Chrysoula Belessi, Neil E. Kay, Frederic Davi, John C. Byrd, Sarka Pospisilova, Jennifer R. Brown, Mark Catherwood, Zadie Davis, David Oscier, Marco Montillo, Livio Trentin, Richard Rosenquist, Paolo Ghia, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Kostas Stamatopoulos, Thomas J. Kipps, Donna Neuberg, Nicholas Chiorazzi
Summary: Patients with mutated IGHV genes (M-CLL) have better outcomes, possibly due to suppressed BCR signaling that no longer delivers trophic signals to leukemic B cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sylwia Chocholska, Michal Zarobkiewicz, Agata Szymanska, Natalia Lehman, Justyna Wos, Agnieszka Bojarska-Junak
Summary: The aim of this study was to investigate the expression of miR-17 similar to 92 cluster members in CLL patients. The study provides new evidence regarding the heterogeneity of miR-17 similar to 92 cluster members' expression in CLL patients. High miR-20a expression can be considered an independent favorable prognostic factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Justyna Wos, Sylwia Chocholska, Wioleta Kowalska, Waldemar Tomczak, Agata Szymanska, Agnieszka Karczmarczyk, Agnieszka Szuster-Ciesielska, Agnieszka Wojciechowska, Agnieszka Bojarska-Junak
Summary: TEMs, characterized by the phenotype of CD14+CD16+Tie2+, have been identified as a new immunosuppressive force in tumors and are associated with unfavorable prognosis in CLL patients. Despite not being an independent predictor of survival, TEM can serve as an important complement to other prognostic indicators in CLL patients.
Article
Oncology
Davide Bagnara, Catherine Tang, Jennifer R. Brown, Siddha Kasar, Stacey Fernandes, Monica Colombo, Stefano Vergani, Andrea N. Mazzarello, Fabio Ghiotto, Silvia Bruno, Fortunato Morabito, Kanti R. Rai, Jonathan E. Kolitz, Jacqueline C. Barrientos, Steven L. Allen, Franco Fais, Matthew D. Scharff, Thomas MacCarthy, Nicholas Chiorazzi
Summary: The analysis of IGHV gene mutations in chronic lymphocytic leukemia has shown that intraclonal heterogeneity exists in almost all CLL clones, with some subclones potentially becoming a significant portion of the disease burden. Additionally, post-transformation IGHV-IGHD-IGHJ heterogeneity is similar in different CLL patient categories, suggesting a common underlying mechanism for clonal evolution.
FRONTIERS IN ONCOLOGY
(2021)
Letter
Hematology
Zuzana Chyra, Tereza Sevikova, Petr Vojta, Janka Puterova, Lucie Brozova, Katerina Growkova, Jana Filipova, Martina Zatopkova, Sebastian Grosicki, Agnieszka Barchnicka, Wieslaw Wiktor-Jedrzejczak, Anna Waszczuk-Gajda, Alexandra Jungova, Aneta Mikulasova, Marian Hajduch, Martin Mokrejs, Ludek Pour, Martin Stork, Lubica Harvanova, Martin Mistrik, Gabor Mikala, Pawel Robak, Anna Czyz, Jakub Debski, Lidia Usnarska-Zubkiewicz, Artur Jurczyszyn, Lukas Stejskal, Gareth Morgan, Fedor Kryukov, Eva Budinska, Michal Simicek, Tomas Jelinek, Matous Hrdinka, Roman Hajek
Article
Hematology
Ceri Bygrave, Charlotte Pawlyn, Faith Davies, Zoe Craig, David Cairns, Anna Hockaday, Matthew Jenner, Gordon Cook, Mark Drayson, Roger Owen, Walter Gregory, Gareth Morgan, Graham Jackson, Martin Kaiser
Summary: Despite equal access to subsequent therapies, myeloma patients who relapse early within 12 months of autologous stem cell transplant have significantly worse progression-free survival and overall survival compared to later relapsing patients, highlighting the urgent need for improved outcome prediction and early intervention strategies.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Graham H. Jackson, Charlotte Pawlyn, David A. Cairns, Alina Striha, Corinne Collett, Anna Waterhouse, John R. Jones, Jamie Wilson, Craig Taylor, Bhuvan Kishore, Mamta Garg, Cathy D. Williams, Kamaraj Karunanithi, Jindriska Lindsay, Matthew W. Jenner, Gordon Cook, Nigel H. Russell, Mark T. Drayson, Martin F. Kaiser, Roger G. Owen, Walter M. Gregory, Faith E. Davies, Gareth J. Morgan
Summary: The Myeloma XI study compared the efficacy of thalidomide and lenalidomide in treating newly diagnosed transplant-ineligible myeloma patients, finding that CRDa had deeper responses for patients aged <= 70 years, but limited tolerability in older, frailer patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Francesco Maura, Ola Landgren, Gareth J. Morgan
Summary: Advancements in next-generation sequencing technology have allowed for a better understanding of the genetic landscape of multiple myeloma, including drivers and evolutionary processes. This new knowledge can be utilized in clinical settings to improve therapeutic interventions at various disease stages.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Graham H. Jackson, Faith E. Davies, Charlotte Pawlyn, David A. Cairns, Alina Striha, Corinne Collett, Anna Waterhouse, John R. Jones, Bhuvan Kishore, Mamta Garg, Cathy D. Williams, Kamaraj Karunanithi, Jindriska Lindsay, David Allotey, Salim Shafeek, Matthew W. Jenner, Gordon Cook, Nigel H. Russell, Martin F. Kaiser, Mark T. Drayson, Roger G. Owen, Walter M. Gregory, Gareth J. Morgan
Summary: The results of the Myeloma XI phase III trial showed that CRD induction therapy resulted in better progression-free survival and overall survival for multiple myeloma patients, while lenalidomide maintenance therapy improved PFS.
Article
Hematology
Charlotte Pawlyn, David A. Cairns, Tom Menzies, John R. Jones, Matthew W. Jenner, Gordon Cook, Kevin D. Boyd, Mark T. Drayson, Martin F. Kaiser, Roger G. Owen, Walter Gregory, Gareth J. Morgan, Graham H. Jackson, Faith E. Davies
Summary: Autologous stem cell transplant (ASCT) is the standard of care for consolidation after induction therapy in newly diagnosed myeloma patients. While older patients may have a reduced progression-free survival after ASCT, the treatment is well tolerated regardless of age. Data from clinical trials and real-world practice suggest that ASCT can benefit selected older myeloma patients.
Article
Oncology
Sarah Bird, David Cairns, Tom Menzies, Kevin Boyd, Faith Davies, Gordon Cook, Mark Drayson, Walter Gregory, Matthew Jenner, John Jones, Martin Kaiser, Roger Owen, Graham Jackson, Gareth Morgan, Charlotte Pawlyn
Summary: There are fundamental differences in genetic lesions underlying the biology of multiple myeloma between males and females, with females more likely to have high-risk disease. However, the impact of sex on patient outcomes is not significant, as progression-free survival and overall survival were similar in both sexes.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Hematology
Kwee L. Yong, Samantha Hinsley, Holger W. Auner, Ceri Bygrave, Martin F. Kaiser, Karthik Ramasamy, Ruth M. de Tute, Debbie Sherratt, Louise Flanagan, Mamta Garg, Stephen Hawkins, Catherine Williams, Jamie Cavenagh, Neil K. Rabin, James Croft, Gareth Morgan, Faith Davies, Roger G. Owen, Sarah R. Brown
Summary: The study compared the efficacy of the proteasome inhibitors carfilzomib and bortezomib in combination with cyclophosphamide and dexamethasone for second-line treatment of myeloma. Carfilzomib showed a higher rate of very good partial response and overall response compared to bortezomib, with carfilzomib maintenance associated with longer progression-free survival.
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
Cell Biology
Francesco Maura, Eileen M. Boyle, Even H. Rustad, Cody Ashby, David Kaminetzky, Benedetto Bruno, Marc Braunstein, Michael Bauer, Patrick Blaney, Yubao Wang, Hussein Ghamlouch, Louis Williams, James Stoeckle, Faith E. Davies, Brian A. Walker, Kylee Maclachlan, Ben Diamond, Ola Landgren, Gareth J. Morgan
Summary: Analysis of the genetic basis for multiple myeloma has provided important insights into disease initiation, progression, and treatment. Chromothripsis, a type of structural variation, plays a critical role in early disease phases and can be used for clinical classification and predicting high-risk patients.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Benedith Oben, Guy Froyen, Kylee H. Maclachlan, Daniel Leongamornlert, Federico Abascal, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Ellen Geerdens, Benjamin T. Diamond, Ingrid Arijs, Brigitte Maes, Kimberly Vanhees, Malin Hultcrantz, Elisabet E. Manasanch, Dickran Kazandjian, Alexander Lesokhin, Ahmet Dogan, Yanming Zhang, Aneta Mikulasova, Brian Walker, Gareth Morgan, Peter J. Campbell, Ola Landgren, Jean-Luc Rummens, Niccolo Bolli, Francesco Maura
Summary: The study demonstrates that MGUS and SMM that do not progress to multiple myeloma have a distinct genomic profile and emerge later in the patient's life.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Kwan Yeung Wong, Gareth J. Morgan, Eileen M. Boyle, Alfred Sze Lok Cheng, Kevin Yuk-Lap Yip, Chor Sang Chim
Summary: Enhancer DNA methylation and MYBPHL expression were studied in multiple myeloma, showing that hypomethylation of CpG1 inside the MYBPHL enhancer was associated with increased MYBPHL expression, potentially implicated in myelomagenesis.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Eileen M. Boyle, Louis Williams, Patrick Blaney, Cody Ashby, Michael Bauer, Brian A. Walker, Hussein Ghamlouch, Jinyoung Choi, Emeline Perrial, Yubao Wang, Jessica Caro, James H. Stoeckle, Arnaldo Arbini, David Kaminetzky, Marc Braunstein, Benedetto Bruno, Beatrice Razzo, Benjamin Diamond, Kylee Maclachlan, Francesco Maura, Ola Landgren, Rachel Litke, Christopher D. Fegan, Johnathan Keats, Daniel Auclair, Faith E. Davies, Gareth J. Morgan
Review
Oncology
Jessica Caro, Marc Braunstein, Louis Williams, Benedetto Bruno, David Kaminetzky, Ariel Siegel, Beatrice Razzo, Serge Alfandari, Gareth J. Morgan, Faith E. Davies, Eileen M. Boyle
Summary: Infection and chronic inflammation play significant roles in plasma cell disorders, and are common complications in these conditions. The use of immune-based therapeutic agents in multiple myeloma requires attention to their impact on infection epidemiology and the development of preventive strategies. Furthermore, infection and pathogens are believed to influence disease biology and the formation of plasma cells.
Article
Oncology
Mark A. Dawson, Gautam Borthakur, Brian J. P. Huntly, Anastasios Karadimitris, Adrian Alegre, Aristeidis Chaidos, Dan T. Vogl, Daniel A. Pollyea, Faith E. Davies, Gareth J. Morgan, Jacob L. Glass, Manali Kamdar, Maria -Victoria Mateos, Natalia Tovar, Paul Yeh, Regina Garcia Delgado, Faisal Basheer, Ludovica Marando, Paolo Gallipoli, Anastasia Wyce, Anu Shilpa Krishnatry, Olena Barbash, Evi Bakirtzi, Geraldine Ferron-Brady, Natalie O. Karpinich, Michael T. McCabe, Shawn W. Foley, Thierry Horner, Arindam Dhar, Brandon E. Kremer, Michael Dickinson
Summary: Molibresib, a selective inhibitor of BET proteins, was evaluated as a monotherapy for hematological malignancies. The study consisted of dose escalation to determine the recommended dose and dose expansion to assess safety and efficacy in relapsed/refractory MDS and CTCL patients. Results showed limited antitumor activity and significant toxicities, suggesting the need for combination regimens with molibresib.
CLINICAL CANCER RESEARCH
(2023)