Article
Chemistry, Medicinal
Hana Votavova, Zuzana Urbanova, David Kundrat, Michaela Dostalova Merkerova, Martin Vostry, Monika Hruba, Jaroslav Cermak, Monika Belickova
Summary: DFX improves hematopoiesis in anemic myelodysplastic syndrome patients by modulating immune response, suppressing negative regulators of blood cell differentiation, and upregulating heme metabolism.
Article
Hematology
Vladimir Riabov, Maximilian Mossner, Alexandra Stoehr, Johann-Christoph Jann, Alexander Streuer, Nanni Schmitt, Antje Knaflic, Verena Nowak, Nadine Weimer, Julia Oblaender, Iris Palme, Christiane Schumann, Claudia D. Baldus, Torsten J. Schulze, Patrick Wuchter, Henning Roehl, Ahmed Jawhar, Christel Weiss, Tobias Boch, Georgia Metzgeroth, Martin Neumann, Wolf-Karsten Hofmann, Florian Nolte, Daniel Nowak
Summary: The expression of ERFE and GDF15 in MDS patients was found to be highly aberrant, with ERFE expression unexpectedly relevant for MDS prognosis. ERFE overexpression predicted superior overall survival in certain MDS subgroups, suggesting a possible involvement of ERFE in the molecular pathogenesis of MDS.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Jessica M. Stempel, Nikolai A. Podoltsev, Talib Dosani
Summary: Myelodysplastic syndromes (MDS) are a group of bone marrow disorders characterized by ineffective hematopoiesis, progressive cytopenias, and the potential to progress to acute myeloid leukemia (AML). The most common causes of morbidity and mortality in MDS patients are complications related to MDS itself rather than progression to AML. Supportive care measures are essential, especially in lower-risk MDS patients with a better prognosis, who require long-term monitoring of disease and treatment-related complications. This review discusses the frequent complications and supportive care interventions in MDS patients, including transfusion support, iron overload management, antimicrobial prophylaxis, considerations in the era of COVID-19, routine immunizations, and palliative care.
Article
Oncology
Mathias Schneeweiss-Gleixner, Georg Greiner, Susanne Herndlhofer, Julia Schellnegger, Maria-Theresa Krauth, Karoline Gleixner, Friedrich Wimazal, Corinna Steinhauser, Michael Kundi, Renate Thalhammer, Ilse Schwarzinger, Gregor Hoermann, Harald Esterbauer, Manuela Fodinger, Peter Valent, Wolfgang R. Sperr
Summary: Although iron overload is a clinical challenge, little is known about the clinical impact of HFE-variants in myelodysplastic syndromes. The study found that HFE-variants H63D and C282Y are frequently detected in Austrian MDS patients, who have higher ferritin levels at diagnosis, accumulate iron slightly faster, and have a better progression-free survival than non-mutated patients.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Medicine, General & Internal
Felicitas Schulz, Ulrich Hauch, Sandra Ketzler-Henkel, Eyck von der Heyde, Michael Koenigsmann, Michael Lauseker, Nora Schulte, Ulrich Germing
Summary: Myelodysplastic syndromes and myeloproliferative neoplasms are hematologic diseases associated with bone marrow failure, and transfusion of red blood cells is necessary but leads to iron overload. Therefore, iron chelation therapy plays a crucial role in anemic patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pediatrics
Rajeswari Rethinaswamy DivakarJose, C. G. Delhikumar, G. Ram Kumar
Summary: The study aimed to evaluate the efficacy and safety of dual oral iron chelation therapy in reducing iron overload in transfusion-dependent thalassemic children. The results showed a significant decrease in serum ferritin levels with the combination therapy, while liver and myocardial iron concentrations did not change significantly. Adverse effects such as red color urine and transient elevation in creatinine and liver enzymes were observed during the study period.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Article
Oncology
Laurent Pascal
Summary: Iron overload is harmful to elderly patients with low-risk myelodysplastic syndromes (MDS), especially those with cardiovascular disease. A randomized study has shown improved event-free survival with Iron Chelation Therapy (ICT) in these patients. Further research is needed to better understand the benefits of ICT.
BULLETIN DU CANCER
(2023)
Article
Chemistry, Medicinal
Mengdie Su, Yanjia Zhao, Mei Li, Chenyang Jia, He Liu, Yue Zhang, Weiwei Li, Ying Peng, Jiang Zheng
Summary: This study identified two hydroxylated metabolites of Deferasirox (DFS) in rat liver microsomes, which were also detected in bile and urine. CYP1A2 and CYP3A4 were found to be the main enzymes responsible for the metabolic activation of DFS. DFS exhibited cytotoxicity towards primary hepatocytes, but pretreatment with ketoconazole and 1-aminobenzotrizole reduced its toxicity.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Chemistry, Analytical
Axel Steinbrueck, Adam C. Sedgwick, Suh-Mi Hwang, Sajal Sen, Michael Y. Zhao, Dan-Ying Huang, Daniel M. Knoll, Yu-Ying Wang, Jonathan L. Sessler
Summary: ExSO(3)H acts as a colorimetric chemosensor for detecting and quantifying Fe3+ in aqueous samples at pH 2-5. It also interacts with human serum albumin to produce a fluorescence turn-on response, which is quenched in the presence of Fe3+, allowing for monitoring of this metal cation via two independent methods.
Review
Hematology
Nina Kim, Steven Pavletic, Kelly J. Norsworthy
Summary: The International Working Group (IWG) response criteria for myelodysplastic syndromes (MDS) have been widely adopted in clinical trials, but clinical experience has revealed limitations and the need for further validation of the endpoints proposed by the IWG.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Medicine, General & Internal
Kathrin Nachtkamp, Guido Kobbe, Norbert Gattermann, Ulrich Germing
Summary: Myelodysplastic syndromes (MDS) are malignant diseases arising from hematopoietic stem cells, with an incidence of 4 cases per 100,000 persons per year. They are usually diagnosed when evaluating cytopenia, and the median survival time is three years. This review summarizes the latest research on the diagnosis and treatment of MDS.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2023)
Review
Oncology
Giuseppe A. Palumbo, Sara Galimberti, Wilma Barcellini, Daniela Cilloni, Nicola Di Renzo, Elena Maria Elli, Carlo Finelli, Luca Maurillo, Alessandra Ricco, Pellegrino Musto, Rodolfo Russo, Roberto Latagliata
Summary: Iron chelation therapy has become a mainstay in heavily transfused hematological patients to reduce iron overload and prevent organ damage. It is widely used in thalassemic patients and low-risk MDS patients, and has been proposed for high-risk MDS patients and other disorders requiring significant transfusion support. Data suggests that iron toxicity exacerbates anemia and clinical comorbidities, and with the availability of approved oral iron chelators, a larger use of ICT is envisioned in the near future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Nan Zhou, Yan Cui, Rui Zhu, Yuhuan Kuang, Wenhui Ma, Jianyuan Hou, Yumeng Zhu, Shubo Chen, Xin Xu, Ke Tan, Pengxiu Cao, Xianglin Duan, Yumei Fan
Summary: This study demonstrated the inhibitory effect of deferasirox (DFX), an oral iron chelator, on cervical cancer. DFX reduced cell viability and induced cell apoptosis in cervical cancer cell lines. It also promoted cell cycle arrest and inhibited cell invasion by regulating key proteins. Additionally, DFX suppressed the activation of Akt and the MEK/ERK signaling pathway, leading to inhibition of tumor growth and reduction of iron deposits and reactive oxygen species levels. These findings suggest that DFX could be a potential therapeutic agent for cervical cancer.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Biology
Alkistis Adramerina, Nikoleta Printza, Emmanouel Hatzipantelis, Symeon Symeonidis, Labib Tarazi, Aikaterini Teli, Marina Economou
Summary: Thalassemia is a hereditary anemia that requires regular blood transfusions and chelation therapy. The new deferasirox film-coated tablet (DFX FCT) offers a more convenient and well-tolerated treatment option, although it may lead to increased adverse events in younger patients. The study confirmed the safety of DFX FCT in older children, but higher doses were required for effective chelation.
Article
Hematology
Julia Stomper, Paulina Richter-Pechanska, Dietmar Pfeifer, Immacolata Andolfo, Achille Iolascon, Martina U. Muckenthaler, Michael Luebbert
Summary: This study describes sustained and dose-dependent erythroid improvement in a patient with constitutional variants in the TRIB2 and ABCB6 genes after treatment with DFX.
Article
Oncology
Francesco Mannelli, Paola Guglielmelli, Paola Fazi, Enrico Crea, Alfonso Piciocchi, Marco Vignetti, Sergio Amadori, Fabrizio Pane, Adriano Venditti, Alessandro M. Vannucchi
Summary: The evolution into a blast phase is a fatal event in myeloproliferative neoplasms, with a median survival of 3-6 months. Clinical trials with innovative approaches are needed for this category of patients. The ENABLE trial aims to test the combination of venetoclax and decitabine in patients with post-MPN blast phase, who have a poor prognosis.
Editorial Material
Oncology
Raffaele Palmieri, Luca Maurillo, Maria Ilaria Del Principe, Giovangiacinto Paterno, Roland Bruno Walter, Adriano Venditti, Francesco Buccisano
Article
Hematology
Luca Guarnera, Gentiana Elena Trotta, Valentina Boldrini, Lucia Cardillo, Ilaria Cerroni, Valeria Mezzanotte, Gianmario Pasqualone, Arianna Savi, Beatrice Borsellino, Elisa Buzzatti, Raffaele Palmieri, Giovangiacinto Paterno, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe
Summary: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined.
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
(2023)
Letter
Hematology
Luca Guarnera, Elisa Buzzatti, Fabrizio Bonanni, Giovangiacinto Paterno, Antonella Riccitelli, Vittorio Forte, Adriano Venditti, Maria Ilaria Del Principe
ANNALS OF HEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Elisa Parciante, Cosimo Cumbo, Luisa Anelli, Antonella Zagaria, Immacolata Redavid, Angela Minervini, Maria Rosa Conserva, Giuseppina Tota, Nicoletta Coccaro, Francesco Tarantini, Crescenzio Francesco Minervini, Maria Giovanna Macchia, Giorgina Specchia, Pellegrino Musto, Francesco Albano
Summary: NLRP3 is an extensively studied inflammasome member that, when overactivated, can drive several carcinomas. It is activated by different signals and plays a crucial role in metabolic disorders, inflammatory diseases, and autoimmune diseases. NLRP3 belongs to the pattern recognition receptors (PRRs) family, is expressed in various immune cells, and primarily functions in myeloid cells. Investigating the NLRP3 inflammasome complex is a novel horizon for exploration, and inhibiting IL-1 beta or NLRP3 could be a beneficial therapeutic strategy for cancer, improving existing protocols.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Elisa Meddi, Arianna Savi, Federico Moretti, Flavia Mallegni, Raffaele Palmieri, Giovangiacinto Paterno, Elisa Buzzatti, Maria Ilaria Del Principe, Francesco Buccisano, Adriano Venditti, Luca Maurillo
Summary: In acute myeloid leukemia (AML), many patients experience relapse despite achieving complete remission. Traditional morphologic criteria are inadequate for assessing treatment response. Quantification of measurable residual disease (MRD) is a strong prognostic marker in AML, with MRD-negative patients having lower relapse rates and better survival. Different techniques for detecting MRD are available, and their use in guiding post-remission therapy is being actively investigated. Despite controversy, the prognostic value of MRD shows promise in supporting drug development and potentially expediting regulatory approval of new agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Maria Rosa Conserva, Immacolata Redavid, Luisa Anelli, Antonella Zagaria, Francesco Tarantini, Cosimo Cumbo, Giuseppina Tota, Elisa Parciante, Nicoletta Coccaro, Crescenzio Francesco Minervini, Angela Minervini, Giorgina Specchia, Pellegrino Musto, Francesco Albano
Summary: One key process controlling leukemogenesis is the regulation of oncogenic gene expression by transcription factors acting as tumor suppressors. In this review, the role of IKAROS and the molecular pathway involving IKZF1 gene lesions in acute leukemias are discussed. IKAROS, as a zinc finger transcription factor, plays a crucial role in hematopoiesis and leukemogenesis by activating or repressing tumor suppressors or oncogenes. The involvement of IKAROS in both acute lymphoblastic leukemia and acute myeloid leukemia suggests its importance in understanding leukemia pathophysiology and developing targeted treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Gianfranco Catalano, Alessandra Zaza, Cristina Banella, Elvira Pelosi, Germana Castelli, Elisabetta de Marinis, Ariela Smigliani, Serena Travaglini, Tiziana Ottone, Mariadomenica Divona, Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Emanuele Ammatuna, Ugo Testa, Clara Nervi, Adriano Venditti, Maria Teresa Voso, Nelida Ines Noguera
Summary: We characterized the metabolic background in different types of Acute Myeloid Leukemia (AML) by comparing the metabolism of primary AML blasts with that of normal hematopoietic progenitors. The AML blasts showed lower respiratory and glycolytic capacities compared to hematopoietic precursors. AML blasts can be grouped based on Proton Leak values, and the group with high Proton Leak and high respiratory capacity had shorter overall survival time and overexpression of MCL1 protein. MCL1 was found to directly bind to HK2 on the outer mitochondrial membrane, suggesting its role in inducing glycolysis and promoting resistance to therapy in AML cells.
Article
Oncology
L. Maurillo, A. Spagnoli, A. Candoni, C. Papayannidis, E. Borlenghi, D. Lazzarotto, L. Fianchi, M. Sciume, M. E. Zannier, F. Buccisano, M. I. Del Principe, V. Mancini, M. Breccia, R. Fanin, E. Todisco, M. Lunghi, R. Palmieri, N. Fracchiolla, P. Musto, G. Rossi, A. Venditti
Summary: This study compared the efficacy of azacitidine and decitabine in elderly patients with untreated AML. The results showed similar outcomes in terms of complete remission, overall survival, and disease free survival between the two groups.
Letter
Medicine, General & Internal
Luca Guarnera, Elisa Buzzatti, Francesco Marchesi, Daniele Armiento, Carla Mazzone, Saveria Capria, Emilia Scalzulli, Francesco Malfona, Sabina Chiaretti, Raffaele Palmieri, Giovangiacinto Paterno, Chiara Franzese, Fabrizio Bonanni, Arianna Savi, Gianmario Pasqualone, Federico Moretti, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe
Article
Oncology
T. Ottone, G. Silvestrini, R. Piazza, S. Travaglini, C. Gurnari, F. Marchesi, A. M. Nardozza, E. Fabiani, E. Attardi, L. Guarnera, M. Divona, P. Ricci, M. A. Irno Consalvo, S. Ienzi, R. Arcese, A. Biagi, L. Fiori, M. Novello, A. Mauriello, A. Venditti, L. Anemona, M. T. Voso
Summary: By analyzing the transcriptome profile of AML patients, researchers found that TWIST1, ECM-receptor interaction, and focal-adhesion pathways were significantly deregulated. The study also showed that metformin can interfere with these processes.
Article
Hematology
Pasquale Niscola, Carla Mazzone, Stefano Fratoni, Nicolina Rita Ardu, Laura Cesini, Marco Giovannini, Tiziana Ottone, Lucia Anemona, Maria Teresa Voso, Paolo de Fabritiis
Summary: We present a rare case of a very old patient with acute myeloid leukemia and disseminated leukemia cutis, containing an NPM1 mutation. The patient achieved a long-lasting molecular complete remission with the azacitidine/venetoclax combination therapy, highlighting its potential value in such cases.
ACTA HAEMATOLOGICA
(2023)
Article
Hematology
Michael Luebbert, Pierre W. Wijermans, Michal Kicinski, Sylvain Chantepie, Walter J. F. M. Van der Velden, Richard Noppeney, Laimonas Griskevicius, Andreas Neubauer, Martina Crysandt, Radovan Vrhovac, Mario Luppi, Stephan Fuhrmann, Ernesta Audisio, Anna Candoni, Olivier Legrand, Robin Foa, Gianluca Gaidano, Danielle van Lammeren-Venema, Eduardus F. M. Posthuma, Mels Hoogendoorn, Anne Giraut, Marian Stevens-Kroef, Joop H. Jansen, Aniek O. de Graaf, Fabio Efficace, Emanuele Ammatuna, Jean-Pierre Vilque, Ralph Waesch, Heiko Becker, Nicole Blijlevens, Ulrich Duehrsen, Frederic Baron, Stefan Suciu, Sergio Amadori, Adriano Venditti, Gerwin Huls
Summary: This study compares the efficacy and safety of decitabine monotherapy with intensive chemotherapy in older patients with acute myeloid leukemia. The results show that 10-day decitabine monotherapy is as effective and safer than 3 + 7 chemotherapy in older patients.
LANCET HAEMATOLOGY
(2023)
