Article
Hematology
Dana Ghergus, Mickael Martin, Anne-Marie Knapp, Fabien Delmotte, Aurelie Joublin-Delavat, Sophie Jung, Jean-Nicolas Schickel, Isabelle Mendel, Arnaud Dupuis, Bernard Drenou, Herve Ghesquieres, Gilles Salles, Lucile Baseggio, Raoul Herbrecht, Anne-Sophie Korganow, Laurent Vallat, Pauline Soulas-Sprauel, Eric Meffre, Thierry Martin
Summary: This study found that ZAP70 is expressed in nonmalignant B cells in CLL patients and is associated with autoimmune cytopenia. This finding contributes to a better understanding of the role of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Andrea N. Mazzarello, Eva Gentner-Goebel, Marcus Duehren-von Minden, Tatyana N. Tarasenko, Antonella Nicolo, Gerardo Ferrer, Stefano Vergani, Yun Liu, Davide Bagnara, Kanti R. Rai, Jan A. Burger, Peter J. McGuire, Palash C. Maity, Hassan Jumaa, Nicholas Chiorazzi
Summary: This study found that IgM plays a critical and selective role in BCR signaling and B cell fate decisions in chronic lymphocytic leukemia (CLL), which may open up new avenues for CLL therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Ana P. Gonzalez-Rodriguez, Angel R. Payer, Esther Gonzalez-Garcia, Alejandro Lopez-Soto, Segundo Gonzalez
Summary: The dysregulation of LAG-3 expression in chronic lymphocytic leukemia (CLL) correlates with poor prognosis, and treatment with anti-LAG-3 monoclonal antibody relatlimab may restore anti-tumor immune responses.
Article
Oncology
Giovanni D'Arena, Candida Vitale, Marta Coscia, Daniela Lamorte, Giuseppe Pietrantuono, Francesca Perutelli, Fiorella D'Auria, Teodora Statuto, Luciana Valvano, Annamaria Tomasso, Valentina Griggio, Rebecca Jones, Giovanna Mansueto, Oreste Villani, Simona D'Agostino, Vito Viglioglia, Vincenzo De Feo, Fabrizio Calapai, Carmen Mannucci, Alessandro Sgambato, Dimitar G. Efremov, Luca Laurenti
Summary: This study found that higher baseline serum levels of soluble CD200 in patients with chronic lymphocytic leukemia (CLL) were associated with more aggressive features and a worse prognosis. While soluble CD200 could predict a worse prognosis and response to chemotherapy, it did not have a significant impact on overall survival in multivariate analysis. The findings support the role of CD200 as a diagnostic tool, prognostic indicator, and potential therapeutic target in CLL.
Article
Pathology
Richa Gupta, Neha Garg, Abha Singh, Shyam Jain
Summary: This study investigated the prevalence of ZAP-70 and its association with other prognostic markers in Indian CLL patients. The results found a low prevalence rate of ZAP-70 and no association with conventional poor prognostic factors. Most patients were in the good prognostic group, suggesting a favorable prognosis and good overall survival. Geographical variations, genetic makeup, and natural history may contribute to these differences.
INDIAN JOURNAL OF PATHOLOGY AND MICROBIOLOGY
(2023)
Article
Hematology
Pau Abrisqueta, Daniel Medina, Guillermo Villacampa, Junyan Lu, Miguel Alcoceba, Julia Carabia, Joan Boix, Barbara Tazon-Vega, Gloria Iacoboni, Sabela Bobillo, Ana Marin-Niebla, Marcos Gonzalez, Thorsten Zenz, Marta Crespo, Francesc Bosch
Summary: This study developed a gene expression-based prediction model for early progression in chronic lymphocytic leukemia (CLL). By analyzing 200 genes related to microenvironment signaling, the CLL15 assay was found to be significantly associated with time to first treatment (TtFT) in both the training and validation cohorts. The CLL15 score demonstrated improved prognostic capacity compared to other indicators, such as IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL.
Review
Biotechnology & Applied Microbiology
Candida Vitale, Jamie Lynn Gibbons, Alessandra Ferrajoli
Summary: In the treatment of chronic lymphocytic leukemia (CLL), newer, more selective BTK inhibitors such as acalabrutinib are gaining interest due to their potential to reduce off-target effects of the drug, thereby minimizing side effects and treatment interruptions. This emerging therapy option has shown promise in clinical trials for both relapsed/refractory and treatment-naive CLL patients.
ONCOTARGETS AND THERAPY
(2021)
Article
Oncology
Maria Joao Baptista, Sivasubramanian Baskar, Erika M. Gaglione, Keyvan Keyvanfar, Inhye E. Ahn, Adrian Wiestner, Clare Sun
Summary: In CLL patients, Ibrutinib treatment increases clonality of the TCR repertoire, with stable TCR clonality in patients with sustained remission and decreased TCR clonality in patients with disease progression. Additionally, T cells from responding patients show cytotoxicity against autologous CLL cells in vitro.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Toby A. Eyre, Satoshi Hori, Talha Munir
Summary: Advancements in targeted therapies have expanded treatment options for chronic lymphocytic leukemia (CLL), offering fixed-duration and continuous treatment paradigms. BCL2 inhibitors (BCL2i) and Bruton's tyrosine kinase (BTK) inhibitors have shown advantages and limitations in different aspects, with ongoing research exploring their combination therapies and treatment decision-making based on minimal residual disease (MRD) status.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Zachary A. Hing, Janek S. Walker, Ethan C. Whipp, Lindsey Brinton, Matthew Cannon, Pu Zhang, Steven Sher, Casey B. Cempre, Fiona Brown, Porsha L. Smith, Claudio Agostinelli, Stefano A. Pileri, Jordan N. Skinner, Katie Williams, Hannah Phillips, Jami Shaffer, Larry P. Beaver, Alexander Pan, Kyle Shin, Charles T. Gregory, Gulcin H. Ozer, Selen A. Yilmaz, Bonnie K. Harrington, Amy M. Lehman, Lianbo Yu, Vincenzo Coppola, Pearlly Yan, Peggy Scherle, Min Wang, Philip Pitis, Chaoyi Xu, Kris Vaddi, Selina Chen-Kiang, Jennifer Woyach, James S. Blachly, Lapo Alinari, Yiping Yang, John C. Byrd, Robert A. Baiocchi, Bradley W. Blaser, Rosa Lapalombella
Summary: PRMT5 plays an important role in the progression of CLL to Richter transformation, and the PRMT5 inhibitor PRT382 shows potential therapeutic value.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ehsan Gharib, Parinaz Nasri Nasrabadi, Gilles A. A. Robichaud
Summary: This study evaluated the potential of circRNA expression profiles as biomarkers for the early detection of CLL using bioinformatic algorithms on verified CLL patient datasets. The diagnostic performance of circRNAs in different CLL sample sets was analyzed and validated, showing better prognostic value than existing clinical risk scales for predicting 5-year overall survival. The identified circRNAs are also involved in cancer-related pathways, which provide therapeutic targets for personalized medicine.
Article
Hematology
Adam S. Kittai, Ying Huang, Kyle A. Beckwith, Seema A. Bhat, David A. Bond, John C. Byrd, Daniel Goldstein, Michael R. Grever, Cecelia Miller, Kerry A. Rogers, Max Yano, Jennifer A. Woyach
Summary: This retrospective analysis found that progression on treatment, higher LDH levels, and lymphadenopathy without lymphocytosis were independent prognostic factors for the development of Richter's Transformation in CLL patients treated with ibrutinib. Additionally, the prognosis for Richter's Transformation remained poor.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Mustafa Nuri Yenerel, Arpad Illes, Neil Kay, Jose A. Garcia-Marco, Anthony Mato, Javier Pinilla-Ibarz, John F. Seymour, Stephane Lepretre, Stephan Stilgenbauer, Tadeusz Robak, Wayne Rothbaum, Raquel Izumi, Ahmed Hamdy, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Summary: In this study, acalabrutinib was found to be noninferior to ibrutinib in terms of progression-free survival in patients with CLL, with a lower incidence of cardiovascular adverse events. This suggests that acalabrutinib may be a more tolerable option for continuous therapy in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yi Miao, Wei Xu, Jianyong Li
Summary: Acalabrutinib, a first-in-class BTK inhibitor, is more selective and has fewer off-target toxicities compared to ibrutinib, and has been approved to treat CLL. Clinical trials have demonstrated the safety and efficacy of acalabrutinib in relapsed/refractory and treatment-naive CLL, with ongoing phase 3 trials comparing acalabrutinib to ibrutinib. Early studies also suggest promising results for acalabrutinib combinations with other therapies in CLL patients.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Oncology
Thi Thuy Nguyen, Nguyen Thanh Nhu, Van Khoi Tran, Tran Thuc Huan Nguyen, Chiou-Feng Lin
Summary: BTKis monotherapy is more effective and safer than combination therapy for CLL/SLL patients, providing longer PFS and improved overall response rate. High-risk patients also benefit from BTKis in terms of PFS, and second-generation BTKis have fewer adverse events. Further studies are necessary to validate these findings and determine the optimal therapy for CLL/SLL patients.
Article
Hematology
Miguel A. Galindo-Campos, Nura Lutfi, Sarah Bonnin, Carlos Martinez, Talia Velasco-Hernandez, Violeta Garcia-Hernandez, Juan Martin-Caballero, Coral Ampurdanes, Ramon Gimeno, Lluis Colomo, Gael Roue, Guillaume Guilbaud, Francoise Dantzer, Pilar Navarro, Matilde Murga, Oscar Fernandez-Capetillo, Anna Bigas, Pablo Menendez, Julian E. Sale, Jose Yelamos
Summary: Dysregulation of the c-Myc oncogene is linked to aggressive tumor progression, and PARP-1 and PARP-2 have opposing influence in c-Myc-driven B-cell lymphoma. PARP-1 deficiency accelerates lymphomagenesis, while genetic deletion of PARP-2 prevents B-cell lymphoma. These findings provide important insights for the design of new PARP-centered therapeutic strategies.
Review
Biochemistry & Molecular Biology
Miranda Fernandez-Serrano, Rene Winkler, Juliana C. Santos, Marguerite-Marie Le Pannerer, Marcus Buschbeck, Gael Roue
Summary: In lymphoid neoplasms, malignant transformation is often associated with somatic mutations in B cells affecting the epigenetic machinery. Consequential alterations in histone modifications lead to disease-specific changes in transcriptional programs. Therapeutic strategies targeting histone methylation and acetylation show promise in improving the prognosis of lymphoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Silvia Saumell, Miranda Fernandez-Serrano, Alba Mesa, Felix Lopez-Cadenas, Leonor Arenillas, Ana Alfonso, Maria Julia Montoro, Antonieta Molero, Pilar Leoz, Victoria Riego, Laura Gallur, Olga Salamero, Mayda Navarrete, Barbara Tazon-Vega, Margarita Ortega, Oscar Reig, Gael Roue, Xavier Calvo, Felipe Prosper, Maria Diez-Campelo, David Valcarcel
Summary: The presence of Micromegakaryocytes (microMKs) in MDS patients indicates poorer outcomes, including lower overall survival rate and higher risk of progression to AML. Additionally, incorporating microMKs into the IPSS-R score can improve accuracy, leading to reclassification of some patients into higher-risk groups.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Matthew Salmon, Helen E. White, Hana Zizkova, Andrea Gottschalk, Eliska Motlova, Nuno Cerveira, Dolors Colomer, Daniel Coriu, Georg N. Franke, Enrico Gottardi, Barbara Izzo, Tomas Jurcek, Thomas Lion, Vivien Schaefer, Claudia Venturi, Paolo Vigneri, Magdalena Zawada, Jan Zuna, Lenka Hovorkova, Jitka Koblihova, Hana Klamova, Marketa Stastna Markova, Dana Srbova, Adela Benesova, Vaclava Polivkova, Daniela Zackova, Jiri Mayer, Ingo Roeder, Ingmar Glauche, Thomas Ernst, Andreas Hochhaus, Katerina Machova Polakova, Nicholas C. P. Cross
Summary: This study found that chronic myeloid leukaemia (CML) patients expressing e14a2 BCR::ABL1 have a faster molecular response to therapy compared to patients expressing e13a2. Technical analysis revealed a slight difference in the amplification ratio and efficiency between the two transcript types, resulting in variations in estimates of residual disease. These findings suggest that the choice of transcript type should be considered for optimal patient management.
Letter
Oncology
Steven H. Swerdlow, Elias Campo, Daniel A. Arber, Mario Cazzola, James R. Cook, Hartmut Doehner, Martin Dreyling, Robert P. Hasserjian, Elaine S. Jaffe, Attilio Orazi, Leticia Quintanilla-Martinez, David W. Scott, Ayalew Tefferi, Jane N. Winter, Andrew D. Zelenetz
Article
Oncology
Sandra Castano-Diez, Monica Lopez-Guerra, Cristina Bosch-Castaneda, Alex Bataller, Paola Charry, Daniel Esteban, Francesca Guijarro, Carlos Jimenez-Vicente, Carlos Castillo-Giron, Albert Cortes, Alexandra Martinez-Roca, Ana Triguero, Jose Ramon Alamo, Silvia Bea, Dolors Costa, Dolors Colomer, Maria Rozman, Jordi Esteve, Marina Diaz-Beya
Summary: Despite emerging molecular information, the outcome of patients with chronic myelomonocytic leukemia (CMML) remains unsatisfactory. This study aimed to explore the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and transformation into acute myeloid leukemia (AML). The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Hypomethylating agents and allogeneic stem cell transplantation (alloSCT) were administered to patients, with varying response rates. Targeted therapies with IDH or FLT3 inhibitors showed promise in specific gene mutation cases. AML transformation occurred in a significant proportion of patients, with changes in gene mutation status observed. Complete molecular characterization can help improve risk stratification and personalize therapy.
Article
Oncology
Melody Caillot, Hadjer Miloudi, Antoine Taly, Nuria Profitos-Peleja, Juliana C. Santos, Marcelo L. Ribeiro, Elsa Maitre, Simon Saule, Gael Roue, Fabrice Jardin, Brigitte Sola
Summary: By studying the impact of XPO1 gene mutation on protein function, it was found that the mutation renders lymphoma cells more sensitive to SINEs drugs. Additionally, the mutation also leads to mistrafficking of transcription factors between the nucleus and cytoplasm, affecting the response to ibrutinib.
MOLECULAR ONCOLOGY
(2023)
Correction
Pathology
Birgitta Sander, Elias Campo, Eric D. Hsi
Review
Pathology
Birgitta Sander, Elias Campo, Eric D. Hsi
Summary: This manuscript reviews the clinicopathologic and biologic features of chronic lymphocytic leukaemia/small lymphocytic lymphoma, B-cell prolymphocytic leukaemia, and mantle cell lymphoma. Discussions focus on incorporating new knowledge into the next classification system.
Review
Cell Biology
Juliana Carvalho Santos, Nuria Profitos-Peleja, Salvador Sanchez-Vinces, Gael Roue
Summary: Primarily recognized as a regulator of cytoskeletal dynamics, RHOA is involved in regulating various cellular functions. Deregulated RHOA activity has been linked to cancer growth and metastasis. Recent genomic studies have identified RHOA mutations in leukemia/lymphoma, suggesting its dual role as a tumor promoter or suppressor. Targeting RHOA signaling may offer potential therapeutic strategies for cancer. This review summarizes the molecular mechanisms of RHOA in immune regulation and hematological neoplasms, and discusses current strategies for modulating its activity in these diseases.
Article
Hematology
Julia Salmeron-Villalobos, Natalia Castrejon-de-Anta, Pilar Guerra-Garcia, Joan Enric Ramis-Zaldivar, Monica Lopez-Guerra, Sara Mato, Dolors Colomer, Francisco Diaz-Crespo, Javier Menarguez, Marta Garrido-Pontnou, Mara Andres, Eugenia Garcia-Fernandez, Margarita Llavador, Gerard Frigola, Noelia Garcia, Blanca Gonzalez-Farre, Idoia Martin-Guerrero, Carmen Garrido-Colino, Itziar Astigarraga, Alba Fernandez, Jaime Verdu-Amoros, Soledad Gonzalez-Muniz, Berta Gonzalez, Veronica Celis, Elias Campo, Olga Balague, Itziar Salaverria
Summary: This study investigated the molecular features of pediatric monomorphic posttransplant lymphoproliferative disorders (PTLDs) and found shared pathogenesis between PTLD-BL and EBV-positive immunocompetent (IMC) BL.
Article
Oncology
Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Ismael Boussaid, Mael Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernandez-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Celine Mazzotti, Herve Avet-Loiseau, Oceane Delos, Justine Bertrand-Michel, Amelie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Remy Castellano, Yves Collette, Francois Vergez, Veronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Recher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Herve Guillou, Gael Roue, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clement Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry
Summary: Although the role of CCAAT-enhancer binding protein α (C/EBPα) in cancer cell and metabolic homeostasis is largely unknown, this study reveals its coordination with FLT3 in lipid anabolism and its regulation of fatty acid biosynthesis and desaturation. Furthermore, FLT3 or C/EBPα inactivation decreases monounsaturated fatty acid incorporation and renders FLT3-mutant AML cells vulnerable to ferroptosis. This finding suggests a promising therapeutic potential for targeting FLT3-mutant AML cells.
Review
Oncology
Francesca Guijarro, Marta Garrote, Neus Villamor, Dolors Colomer, Jordi Esteve, Monica Lopez-Guerra
Summary: In recent years, advances in understanding AML pathogenesis and technological progress have led to improved diagnosis and follow-up of AML patients. A combination of immunophenotyping, cytogenetic and molecular studies, including NGS gene panels, is required for AML diagnosis. Multiparametric flow cytometry and quantitative PCR/RT-PCR are currently the most implemented methods for MRD evaluation, but new tools like NGS and digital PCR are needed due to their limitations. This review provides an overview of the technologies used for AML diagnosis and MRD monitoring and highlights the limitations and challenges of current versus emerging tools.
Review
Hematology
Marcelo Lima Ribeiro, Salvador Sanchez Vinces, Laura Mondragon, Gael Roue
Summary: Non-Hodgkin's lymphomas (NHLs) are a diverse group of diseases characterized by heterogeneous molecular features and clinical manifestations. Epigenetic dysregulations, including mutations in epigenetic enzymes, are prevalent in both B-cell and T-cell lymphomas. Over the past decade, a large number of epigenetic-modifying agents have been developed and introduced in clinical management of NHLs.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Oncology
J. Carvalho Santos, N. Profitos Peleja, M. Caillot, S. Sanchez Vinces, B. Sola, M. Lima Ribeiro, G. Roue
EUROPEAN JOURNAL OF CANCER
(2022)