Article
Cell Biology
Yuqian Zhu, Dandan Song, Juan Guo, Jiacheng Jin, Ying Tao, Zheng Zhang, Feng Xu, Qi He, Xiao Li, Chunkang Chang, Lingyun Wu
Summary: The study found that U2AF1 mutations are associated with poor prognosis in MDS and AML patients, significantly inhibiting cell proliferation and inducing cellular apoptosis in cell models. The results showed that U2AF1 mutations promoted FOXO3a-dependent apoptosis and NLRP3 inflammasome activation, leading to pyroptotic cell death. FOXO3a was identified as the key molecule on which these pathways converge.
CELL DEATH & DISEASE
(2021)
Article
Hematology
Rami Komrokji, Luis E. Aguirre, Najla Al Ali, Mohamad Hussaini, David Sallman, Dana Rollison, Eric Padron
Summary: Hemolysis is a significant clinical feature in some patients with myelodysplastic syndromes (MDS). It is often caused by ineffective erythropoiesis or acquired defects in red blood cell (RBC) membrane. This study found that 10% of MDS patients had hemolysis, which was mostly nonimmune. Patients with hemolysis had lower survival rates, decreased response to erythropoiesis-stimulating agents, and higher response to hypomethylating agents. They also had higher prevalence of U2AF1 and EZH2 hotspot mutations, suggesting a role of splicing factor mutations in the development of hemolysis in MDS.
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
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)
Review
Cell Biology
Juan Jose Rodriguez-Sevilla, Vera Adema, Guillermo Garcia-Manero, Simona Colla
Summary: Myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). HMA-based therapy is the standard treatment for MDS, but nearly 50% of patients do not respond. For MDS patients who have failed HMA therapy, clinical trials of experimental agents offer their only chance for improved outcomes. New therapies targeting molecular alterations, cell death regulators, signaling pathways, and immune regulatory proteins have been developed for these patients based on a better understanding of the molecular and biological mechanisms underlying MDS pathogenesis.
CELL REPORTS MEDICINE
(2023)
Review
Oncology
Yangjing Zhao, Weili Cai, Ye Hua, Xiaochen Yang, Jingdong Zhou
Summary: U2AF1 mutation is an important genetic driver event in myelodysplastic syndromes and myeloid malignancies, impacting hematopoiesis, tumor progression, disease prognosis, and leukemic transformation. This review provides a comprehensive overview of the oncogenic role of U2AF1 mutation in myeloid tumors and highlights its potential as a prognostic biomarker and therapeutic target.
Article
Multidisciplinary Sciences
Tatsuya Konishi, Daichi Sadato, Takashi Toya, Chizuko Hirama, Yuya Kishida, Akihito Nagata, Yuta Yamada, Naoki Shingai, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Kyoko Haraguchi, Yoshiki Okuyama, Hironori Harada, Kazuteru Ohashi, Yuka Harada, Noriko Doki
Summary: This study analyzed gene mutations and copy number alterations in younger MDS patients and found that these genetic abnormalities can predict clinical outcomes. Higher-risk patients had lower survival rates and higher relapse rates.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Sheng-Yu Hung, Chien-Chin Lin, Chia-Lang Hsu, Chi-Yuan Yao, Yu-Hung Wang, Cheng-Hong Tsai, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien
Summary: The study revealed that high expression of KIAA0125 in MDS patients is associated with high-risk MDS, ASXL1 and NRAS mutations, and poor prognosis. Multivariate analysis indicated that high KIAA0125 expression independently predicts unfavorable overall survival and leukemia-free survival in MDS patients. Furthermore, global gene expression profile analysis suggested that higher KIAA0125 expressions are closely associated with leukemia stem cell signatures.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Tommaso Matteuzzi, Claudia Sala, Ettore Mosca, Chiara Chiereghin, Noemi Di Nanni, Matteo Gnocchi, Matteo Zampini, Marianna Rossi, Giulia Maggioni, Alberto Termanini, Emanuele Angelucci, Massimo Bernardi, Lorenza Borin, Benedetto Bruno, Francesca Bonifazi, Valeria Santini, Andrea Bacigalupo, Maria Teresa Voso, Esther Oliva, Marta Riva, Marta Ubezio, Lucio Morabito, Alessia Campagna, Claudia Saitta, Victor Savevski, Enrico Giampieri, Daniel Remondini, Francesco Passamonti, Fabio Ciceri, Niccolo Bolli, Alessandro Rambaldi, Wolfgang Kern, Shahram Kordasti, Francesc Sole, Laura Palomo, Guillermo Sanz, Armando Santoro, Uwe Platzbecker, Pierre Fenaux, Luciano Milanesi, Torsten Haferlach, Gastone Castellani, Matteo G. Della Porta
Summary: The study identified eight distinct subgroups of MDS based on specific genomic features, each with different prognostic outcomes. By integrating clinical and genomic variables, a novel prognostic model was developed to provide personalized survival predictions for MDS patients. This model significantly improved the accuracy of current prognostic tools and has the potential to revolutionize disease classification and prognosis in the future.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Pathology
Hong Fang, Sa A. Wang, Wei Xie, Zhenya Tang, Shimin Hu, Savitri Krishnamurthy, L. Jeffrey Medeiros, Wei Wang
Summary: This study reports on 6 patients with myelodysplastic syndrome (MDS) who underwent lymph node biopsies showing MDS infiltration, with distorted architecture and myeloid cell expansion. Despite treatment, all patients had poor responses and short survival times.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
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.
Article
Oncology
Claudia Tregnago, Maddalena Benetton, Davide Padrin, Katia Polato, Giulia Borella, Ambra Da Ros, Anna Marchetti, Elena Porcu, Francesca Del Bufalo, Cristina Mecucci, Franco Locatelli, Martina Pigazzi
Summary: In this study, NPM1 mutations in AML were classified into A-like and non-A-like mutations based on the loss of tryptophan residues, revealing different biological features and sensitivity to chemotherapy. The differential expression of HOXA and HOXB genes and cell death pathways between these two types of mutations suggests the potential for further sub-classification and personalized management of NPM1-mutated AML patients.
Article
Biotechnology & Applied Microbiology
Nida Anwar, Faheem Ahmed Memon, Saba Shahid, Muhammad Shakeel, Muhammad Irfan, Aisha Arshad, Arshi Naz, Ikram Din Ujjan, Tahir Shamsi
Summary: Sequencing studies on MDS patients in Pakistan revealed various genetic mutations associated with myeloid malignancies, including mutations not previously observed in MDS or AML. These findings highlight the importance of molecular profiling in diagnosis and treatment of MDS patients in countries with limited resources like Pakistan. Further research with larger sample sizes is necessary to compare molecular characteristics between Asian and global populations.
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.
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.
