Article
Biochemistry & Molecular Biology
Keli Lima, Maria Fernanda Lopes Carvalho, Diego Antonio Pereira-Martins, Frederico Lisboa Nogueira, Livia Bassani Lins de Miranda, Mariane Cristina do Nascimento, Rita de Cassia Cavaglieri, Jan Jacob Schuringa, Joao Agostinho Machado-Neto, Eduardo Magalhaes Rego
Summary: The study identified the correlation between the expression of phosphatidylinositol-5-phosphate 4-kinase type 2 (PIP4K2) and the response to antineoplastic agents in acute myeloid leukemia (AML). High levels of PIP4K2A were associated with resistance to venetoclax. The combination of THZ-P1-2 and venetoclax showed synergistic effects in AML cells and modulated multiple genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Magdalena Ruiz, Kriti Jindal, Vicky Casey, Luana Margotto Soares, Fil Manuguid, Thomas Moehler
Summary: This study explores the use of novel agents as first-line treatment for AML patients. The results indicate that these agents are increasingly being incorporated into patient care, particularly for patients with specific gene alterations and comorbidities.
Review
Oncology
Sargam Kapoor, Grace Champion, Aparna Basu, Anu Mariampillai, Matthew J. Olnes
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow with poor prognosis. Recent advancements in immune therapies, including immune suppressive therapy and novel treatments like monoclonal antibodies and cellular therapeutics, have shown promise in treating these diseases.
Review
Oncology
A. Bazinet, H. M. Kantarjian
Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Personalized therapy based on patient characteristics and cytogenetic/molecular features is now possible. Intensive or low-intensity treatment approaches can be selected based on patient age and/or comorbidities. Molecularly defined AML subtypes benefit from targeted agents, while novel therapies are needed for TP53-mutated AML. Optimization of AML therapy in patients without actionable mutations and the role of measurable residual disease in modifying therapy are also discussed.
ANNALS OF ONCOLOGY
(2023)
Article
Toxicology
Catarina Sofia Mateus Reis-Silva, Paola Cristina Branco, Keli Lima, Fabiana Lima Silva, Paulo Roberto Hrihorowitsch Moreno, Victor Guallar, Leticia Veras Costa-Lotufo, Joao Agostinho Machado-Neto
Summary: Acute myeloid leukemia (AML) often relapses due to chemoresistance, necessitating new therapeutic strategies. Combination treatment of Venetoclax and Embelin has been shown to enhance cytotoxic effects in AML cell lines, promoting apoptosis.
TOXICOLOGY IN VITRO
(2021)
Article
Immunology
Roberto Limongello, Andrea Marra, Antonella Mancusi, Samanta Bonato, Eni Hoxha, Loredana Ruggeri, Susanta Hui, Andrea Velardi, Antonio Pierini
Summary: Adverse genetic risk acute myeloid leukemia (AML) poses a significant treatment challenge with poor outcomes, necessitating novel therapeutic approaches. While allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative option, high relapse rates and dismal outcomes prompt the exploration of new transplant strategies. Recent research has shown that haploidentical allo-HSCT combined with T cell adoptive immunotherapy can overcome chemoresistance and improve survival in AML patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Rahul S. S. Bhansali, Keith W. W. Pratz, Catherine Lai
Summary: Acute myeloid leukemia (AML), the most common acute leukemia in adults, has seen significant advancements in understanding its molecular profile and treatment options in the past decade. The classification of AML subtypes has shifted from morphology to molecular and genetic basis, leading to improved outcomes with low-intensity induction therapy and targeted oral therapies. However, challenges remain in sequencing and combining therapies, as well as addressing poor prognosis in certain subtypes like TP53 mutations. This review discusses recent updates in AML classification, low-intensity and novel oral combination therapies, and ongoing translational advances for high-risk disease subtypes.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Review
Oncology
Claudio Cerchione, Alessandra Romano, Naval Daver, Courtney DiNardo, Elias Joseph Jabbour, Marina Konopleva, Farhad Ravandi-Kashani, Tapan Kadia, Maria Paola Martelli, Alessandro Isidori, Giovanni Martinelli, Hagop Kantarjian
Summary: The discovery of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2 has led to the development of individualized treatment strategy in approximately 20% of patients with acute myeloid leukemia (AML). Targeting IDH to promote differentiation and maturation of malignant clone is an emerging strategy in AML, and small molecule inhibitors have shown promising efficacy in phase I/II trials. The contribution of IDH1/IDH2 mutations in leukemogenesis and progress of targeted therapeutics in AML is highlighted in this review.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Mark Gurney, Michael O'Dwyer
Summary: CAR-NK cells, as an alternative cell therapy, offer advantages such as rapid availability and potentially fewer side effects, making them particularly suitable for the treatment of acute myeloid leukemia (AML). Research indicates that this therapy has the potential to be a new option for AML treatment.
Review
Oncology
Khashayar Ahmadmehrabi, Ali R. Haque, Ahmed Aleem, Elizabeth A. Griffiths, Gregory W. Roloff
Summary: Acute myeloid leukemia (AML) is a predominantly fatal blood cancer, and treatment options remained stagnant for forty years until recently multiple new agents were approved. These new therapies mainly function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival, and have been approved both as single agents and in combination with conventional chemotherapeutics.
Review
Biochemistry & Molecular Biology
Bernhard Moser, Sophie Edtmayer, Agnieszka Witalisz-Siepracka, Dagmar Stoiber
Summary: Aberrant JAK-STAT signaling in acute myeloid leukemia (AML) plays a crucial role in disease pathogenesis. Targeting the JAK-STAT pathway, particularly constitutively activated STAT3 and STAT5, has shown promising results in vitro and in vivo. Ongoing development of new JAK-STAT inhibitors with better disease specificity offers potential for improved disease management.
Review
Oncology
Linus Angenendt, Jan-Henrik Mikesch, Christoph Schliemann
Summary: The development of antibody-based therapeutics for patients with acute myeloid leukemia has been challenging due to the shared expression of antigens on leukemic blasts and hematopoietic stem and progenitor cells. However, recent years have seen the approval of the first antibody-drug conjugate for AML treatment, and promising results from other antibody-based therapeutics in clinical trials.
CANCER TREATMENT REVIEWS
(2022)
Article
Medicine, Research & Experimental
Joan So, Alexander C. Lewis, Lorey K. Smith, Kym Stanley, Rheana Franich, David Yoannidis, Lizzy Pijpers, Pilar Dominguez, Simon J. Hogg, Stephin J. Vervoort, Fiona C. Brown, Ricky W. Johnstone, Gabrielle McDonald, Danielle B. Ulanet, Josh Murtie, Emily Gruber, Lev M. Kats
Summary: The study reveals that DHODH inhibitors have potent and selective activity against AML, and can reverse the differentiation block in AML cells. In addition, the elimination of the CDK5 gene increases the sensitivity of AML cells to DHODHi.
EMBO MOLECULAR MEDICINE
(2022)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Letter
Oncology
Loic Vasseur, Remi Favier, Rathana Kim, Florence Rabian, Aurelie Cabannes-Hamy, Bruno Cassinat, Nabih Maslah, Nadia Vasquez, Emmanuelle Clappier, Jean-Jacques Kiladjian, Nicolas Boissel
PEDIATRIC BLOOD & CANCER
(2023)
Letter
Hematology
Linus Angenendt, Christoph Roellig, Pau Montesinos, Farhad Ravandi, Gunnar Juliusson, Christian Recher, Raphael Itzykson, Zdenek Racil, Andrew H. Wei, Christoph Schliemann
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)
Article
Oncology
Raphael Itzykson, Valeria Santini, Sylvain Thepot, Lionel Ades, Cendrine Chaffaut, Aristoteles Giagounidis, Margot Morabito, Nathalie Droin, Michael Luebbert, Rosa Sapena, Stanislas Nimubona, Jean Goasguen, Eric Wattel, Gina Zini, Jose Miguel Torregrosa Diaz, Ulrich Germing, Anna Maria Pelizzari, Sophie Park, Nadja Jaekel, Georgia Metzgeroth, Francesco Onida, Robert Navarro, Andrea Patriarca, Aspasia Stamatoullas, Katharina Goetze, Martin Puttrich, Sandra Mossuto, Eric Solary, Silke Gloaguen, Sylvie Chevret, Fatiha Chermat, Uwe Platzbecker, Pierre Fenaux
Summary: This study compared two treatment methods for chronic myelomonocytic leukemia and found that using DAC significantly reduced the risk of CMML transforming into acute myelomonocytic leukemia.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Imene Bousahba, Jeremie David, Florence Castelli, Celine Chollet, Sadia Ouzia, Francois Fenaille, Didier Remond, Nathalie Poupin, Sergio Polakof
Summary: Obesity is a major contributor to the development of type 2 diabetes. This study aims to identify early phenotypes that precede T2D in diet-induced obese minipigs. Through analysis of various parameters, four distinct phenotypes were differentiated, and specific metabolomic signatures were identified in insulin resistant and progressively obese minipigs, potentially serving as biomarkers for early progression to T2D.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Letter
Hematology
Reinaldo Dal Bello, Kim Pacchiardi, Clementine Chauvel, Lionel Ades, Thorsten Braun, Justine Pasanisi, Elise Fournier, Celine Berthon, Emmanuelle Clappier, Emmanuel Raffoux, Delphine Lebon, Thomas Cluzeau, Christophe Roumier, Adriana Plesa, Karine Celli-Lebras, Herve Dombret, Claude Preudhomme, Stephanie Mathis, Alexandre Puissant, Claude Gardin, Raphael Itzykson
Article
Gastroenterology & Hepatology
Emmanuel Weiss, Carlos de la Pena-Ramirez, Ferran Aguilar, Juan-Jose Lozano, Cristina Sanchez-Garrido, Patricia Sierra, Pedro Izquierdo-Bueno Martin, Juan Manuel Diaz, Francois Fenaille, Florence A. Castelli, Thierry Gustot, Wim Laleman, Agustin Albillos, Carlo Alessandria, Marco Domenicali, Paolo Caraceni, Salvatore Piano, Faouzi Saliba, Stefan Zeuzem, Alexander L. Gerbes, Julia A. Wendon, Christian Jansen, Wenyi Gu, Maria Papp, Raj Mookerjee, Carmine Gabriele Gambino, Cesar Jimenez, Ilaria Giovo, Giacomo Zaccherini, Manuela Merli, Antonella Putignano, Frank Erhard Uschner, Thomas Berg, Tony Bruns, Christian Trautwein, Alexander Zipprich, Rafael Banares, Jose Presa, Joan Genesca, Victor Vargas, Javier Fernandez, Mauro Bernardi, Paolo Angeli, Rajiv Jalan, Joan Claria, Christophe Junot, Richard Moreau, Jonel Trebicka, Vicente Arroyo
Summary: This study aimed to identify metabolites associated with short-term death in patients with acutely decompensated cirrhosis and design metabolomic prognostic models. Three prognostic metabolites strongly associated with death were selected and two models were built, which were found to be more accurate in predicting death within 7, 14, and 28 days compared to traditional scoring systems.
Article
Oncology
Nicolas Duployez, Loic Vasseur, Rathana Kim, Laetitia Largeaud, Marie Passet, Anais L'Haridon, Pierre Lemaire, Laurene Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli-Lebras, Lionel Ades, Delphine Lebon, Celine Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Recher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Herve Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme
Summary: Tandem duplications (TDs) of the UBTF gene are found in both pediatric and adult acute myeloid leukemia (AML), with a frequency of 3% in adult patients. Adult patients with UBTF-TD AML have distinct characteristics, such as young age, low bone marrow blast infiltration, and high rates of WT1 mutations, FLT3-ITDs, and trisomy 8. These patients also have lower complete remission rates and similar survival outcomes compared to ELN 2022 intermediate/adverse risk patients. The study highlights the importance of recognizing UBTF-TD AML as a distinct entity in adults.
Article
Chemistry, Analytical
Hong-Dar Lin, Tung-Hsin Lee, Chou-Hsien Lin, Hsin-Chieh Wu
Summary: Multifocal glasses can correct both nearsighted and farsighted vision on the same lens. This research proposes an automatic deformation defect detection system for multifocal glasses, and quantifies the severity of deformation using fuzzy inference and a genetic algorithm.
Article
Immunology
Karine Adel-Patient, Florence Campeotto, Marta Grauso, Blanche Guillon, Marco Moroldo, Eric Venot, Celine Dietrich, Francois Machavoine, Florence A. A. Castelli, Francois Fenaille, Thierry Jo Molina, Patrick Barbet, Christophe Delacourt, Maria Leite-de-Moraes, Guillaume Lezmi
Summary: This study provides a detailed description of local immunological and molecular components of EoE in children and identifies potential circulating EoE biomarkers. The results indicate that EoE is associated with dysregulation of both innate and adaptive immunity, as well as altered pathways related to epithelial cells and barrier functions. Combining metabolomics and cytokines data may offer a set of potential plasma biomarkers for EoE diagnosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Loic Vasseur, Laurene Fenwarth, Jerome Lambert, Stephane de Botton, Martin Figeac, Celine Villenet, Mael Heiblig, Pierre-Yves Dumas, Christian Recher, Celine Berthon, Emilie Lemasle, Delphine Lebon, Juliette Lambert, Christine Terre, Karine Celli-Lebras, Herve Dombret, Claude Preudhomme, Meyling Cheok, Raphael Itzykson, Nicolas Duployez
Summary: The expression of LSC17 gene is associated with risk stratification and measurable residual disease in AML patients, and high LSC17 expression is related to poor treatment response and shorter survival.
Review
Oncology
Shuchi Agrawal-Singh, Jaana Bagri, Nathalie Sakakini, Brian J. P. Huntly
Summary: This article discusses the critical role of leukemia stem cells (LSCs) in the growth of hematological malignancies, emphasizing the importance of integrating epigenetic and genetic information to understand heterogeneity among patients. The article also explores efforts to identify mechanisms of resistance through longitudinal analysis of patient samples and highlights the potential of targeting aberrant epigenetic processes for better therapeutic outcomes and potentially eradicating LSCs.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Rathana Kim, Hugo Bergugnat, Lise Larcher, Matthieu Duchmann, Marie Passet, Stephanie Gachet, Wendy Cuccuini, Marina Lafage-Pochitaloff, Cedric Pastoret, Nathalie Grardel, Vahid Asnafi, Beat W. Schaefer, Eric Delabesse, Raphael Itzykson, Lionel Ades, Yosr Hicheri, Yves Chalandon, Carlos Graux, Patrice Chevallier, Mathilde Hunault, Thibaut Leguay, Francoise Huguet, Veronique Lheritier, Herve Dombret, Jean Soulier, Philippe Rousselot, Nicolas Boissel, Emmanuelle Clappier
Summary: Low hypodiploidy is a common subtype of B-cell acute lymphoblastic leukemia (B-ALL) in older adults, characterized by somatic TP53 biallelic alteration. The study reveals a link between aging and low hypodiploidy ALL, with TP53-mutant clonal hematopoiesis serving as a preleukemic reservoir that can give rise to aneuploidy and B-ALL.
BLOOD CANCER DISCOVERY
(2023)