Review
Genetics & Heredity
Chiara Chiereghin, Erica Travaglino, Matteo Zampini, Elena Saba, Claudia Saitta, Elena Riva, Matteo Bersanelli, Matteo Giovanni Della Porta
Summary: Myelodysplastic syndromes (MDS) are clonal diseases driven by a complex combination of genetic mutations, resulting in ineffective hematopoiesis and an increased risk of progression to acute myeloid leukemia. These mutations can be categorized into a limited number of cellular pathways, influencing clinical phenotype, disease progression, and prognosis.
Review
Biochemistry & Molecular Biology
Veronica Vallelonga, Francesco Gandolfi, Francesca Ficara, Matteo Giovanni Della Porta, Serena Ghisletti
Summary: Inflammation has a significant impact on human hematopoiesis, particularly in regulating the homeostasis of hematopoietic stem cells. Dysregulated inflammation can lead to abnormal hematopoiesis and may be involved in the pathogenesis of diseases such as myelodysplastic syndromes. Recent studies have used single-cell sequencing and multi-omic approaches to investigate the cellular heterogeneity and gene expression of hematopoietic stem cells in normal and malignant conditions, shedding light on the mechanisms underlying inflammatory signaling and immune response activation in MDS progression.
Article
Oncology
Michaela Fontenay, Ismael Boussaid, Nicolas Chapuis
Summary: During aging, low-frequency mutations in hematopoietic cells or clonal hematopoiesis contribute to the development of hematological diseases and cardiovascular diseases. Inflammation associated with age affects clonal evolution and immune response. In turn, mutated hematopoietic cells create an inflammatory bone marrow environment that facilitates their expansion, leading to diverse phenotypes.
BULLETIN DU CANCER
(2023)
Article
Oncology
Claudio Fozza, Andrea Murtas, Giovanni Caocci, Giorgio La Nasa
Summary: Around one third of MDS patients have concomitant AD, but the burden of this association varies in different studies, possibly due to variations in selecting MDS patients and AD subtypes. The prognostic implications and therapeutic approaches for this patient subgroup are still debated.
Review
Medicine, General & Internal
Tzu-Hua Chen-Liang
Summary: This review provides an overview of the most commonly used prognostic scoring systems for MDS patients and discusses the prognostic impact of somatic mutations in this patient population.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Oncology
Giulio Cassanello, Raffaella Pasquale, Wilma Barcellini, Bruno Fattizzo
Summary: This review article discusses the development of novel therapies for patients with myelodysplastic syndromes (MDS), including drugs aimed at improving hematopoiesis and differentiation, hypomethylating agents, compounds targeting intracellular pathways, and immunotherapies. The current management of MDS relies on risk stratification and has limited options for patients with treatment failure. Recent advances in genetic mutations and intracellular pathways are improving disease risk stratification and highlighting therapeutic targets. Several drugs are under evaluation for MDS patients, which differ in mechanism of action, efficacy, and development phase.
Editorial Material
Hematology
Carolien Duetz, David G. J. Cucchi, Tobias B. Polak, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Elihu H. Estey, Arjan A. van de Loosdrecht
Summary: Our study found that most patients with myelodysplastic syndromes (MDS) require therapeutic intervention, but there is a lack of approved treatments. Success rates in MDS trials are low, taking longer to complete compared to average clinical trials, with many trials failing to adequately evaluate important factors like quality of life.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Oncology
Yan Jiang, Su-Jun Gao, Benoit Soubise, Nathalie Douet-Guilbert, Zi-Ling Liu, Marie-Berengere Troadec
Summary: Gene variants, particularly TP53 mutations, play a crucial role in the prognosis of myelodysplastic syndromes (MDS), being associated with higher risk categories, resistance to traditional therapies, rapid leukemic transformation, and poor outcomes. Current prognosis classification systems for MDS do not consider gene variants, but the impact is significant on the clinical heterogeneity and prognosis of the disease.
Article
Pharmacology & Pharmacy
Ran-ran Wang, Tian-yi Yuan, Jian-mei Wang, Yu-cai Chen, Jiu-liang Zhao, Meng-tao Li, Lian-hua Fang, Guan-hua Du
Summary: In PAH, inflammation plays a crucial role in the initiation and maintenance of vascular remodeling, with high levels of inflammatory mediators present in both patients and experimental models. Immune cells are also found to accumulate in and around remodeled pulmonary vessels. Furthermore, autoimmune diseases may contribute to PAH through chronic inflammation and the presence of circulating autoantibodies, suggesting a potential role for anti-inflammatory and immunotherapy in the treatment of PAH.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Hematology
Nathan Radakovich, Manja Meggendorfer, Luca Malcovati, C. Beau Hilton, Mikkael A. Sekeres, Jacob Shreve, Yazan Rouphail, Wencke Walter, Stephan Hutter, Anna Galli, Sara Pozzi, Chiara Elena, Eric Padron, Michael R. Savona, Aaron T. Gerds, Sudipto Mukherjee, Yasunobu Nagata, Rami S. Komrokji, Babal K. Jha, Claudia Haferlach, Jaroslaw P. Maciejewski, Torsten Haferlach, Aziz Nazha
Summary: By utilizing clinical and next-generation sequencing data, a machine learning model was successfully developed for the diagnosis of myeloid malignancies independent of bone marrow biopsy data in an international patient cohort, achieving high performance. The model interpretations suggest that it relies on factors similar to those used by clinicians, and associations between NGS findings and clinically important phenotypes were described. The use of machine learning algorithms to elucidate clinicogenomic relationships was also introduced.
Review
Medicine, General & Internal
Chloe Friedrich, Olivier Kosmider
Summary: This article discusses the role of the mesenchymal niche in the pathophysiology of Myelodysplastic syndromes (MDS) and provides an overview of currently available in vitro and in vivo models that can be used to study the effects of the mesenchymal niche on hematopoietic stem cells (HSCs).
Review
Gastroenterology & Hepatology
Sohaib Khalid Hashmi, Rachel Helen Ceron, Robert O. Heuckeroth
Summary: Visceral smooth muscle is crucial for the movement of hollow organs and has unique properties that facilitate strong contraction and dilation. Visceral myopathies, such as MMIHS and myopathic CIPO, are caused by mutations in cytoskeletal proteins and can lead to severe dysfunction in bowel, bladder, and uterus, with potential fatal consequences.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Oncology
Mikkael A. Sekeres, Nina Kim, Amy E. DeZern, Kelly J. Norsworthy, Jacqueline S. Garcia, R. Angelo de Claro, Marc R. Theoret, Emily Y. Jen, Lori A. Ehrlich, Amer M. Zeidan, Rami S. Komrokji
Summary: MDS drug development faces challenges in biology, trial design, and endpoints. To meet patient needs, approaches to improve MDS drug development should consider disease evolution, patient age, and real-world treatment conditions.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Antonio Cristiano, Riccardo Belardi, Hajro Hajrullaj, Emiliano Fabiani, Giulia Falconi, Elisa Galossi, Sergio Bernardini, Maria Teresa Voso, Marzia Nuccetelli
Summary: This study evaluated the autoimmune profile of Myelodysplastic Syndromes (MDS) and correlated it with the mutational landscape, aiming to identify a molecular-genetic trigger agent related to Systemic Inflammatory Autoimmune Diseases (SIAD).
INFLAMMATION RESEARCH
(2023)
Article
Medicine, General & Internal
Alessia Campagna, Daniela De Benedittis, Luana Fianchi, Emilia Scalzulli, Lorenzo Rizzo, Pasquale Niscola, Anna Lina Piccioni, Ambra Di Veroli, Stefano Mancini, Nicoletta Villiva, Tiziano Martini, Sara Mohamed, Ida Carmosino, Marianna Criscuolo, Susanna Fenu, Maria Antonietta Aloe Spiriti, Francesco Buccisano, Marco Mancini, Agostino Tafuri, Massimo Breccia, Antonella Poloni, Roberto Latagliata
Summary: Patients with isolated del20q in myelodysplastic syndromes show distinct clinical and prognostic features, including older age, predominantly male, low bone marrow blast percentage, and lower platelet count. In terms of treatment, the majority receive erythropoiesis-stimulating agents, while a small portion progress to acute myeloid leukemia. The median overall survival is 60.6 months, with a 5-year cumulative survival rate of 55.9%.
JOURNAL OF CLINICAL MEDICINE
(2022)
