Article
Oncology
Nanni Schmitt, Johann-Christoph Jann, Eva Altrock, Johanna Flach, Justine Danner, Stefanie Uhlig, Alexander Streuer, Antje Knaflic, Vladimir Riabov, Qingyu Xu, Arwin Mehralivand, Iris Palme, Verena Nowak, Julia Oblaender, Nadine Weimer, Verena Haselmann, Ahmed Jawhar, Ali Darwich, Cleo-Aron Weis, Alexander Marx, Laurenz Steiner, Mohamad Jawhar, Georgia Metzgeroth, Tobias Boch, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak
Summary: Preclinical research utilizing a patient-derived xenograft (PDX) model for myelodysplastic syndromes (MDS) demonstrates the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. The study shows that eltrombopag effectively promotes thrombopoiesis in MDS PDX without impacting patients' clonal composition, suggesting the PDX model as a valuable tool for testing new therapeutic concepts in MDS before clinical trials.
Article
Multidisciplinary Sciences
Nanfang Huang, Yang Song, Wenhui Shi, Juan Guo, Lingyun Wu, Zheng Zhang, Qi He, Xiao Li, Feng Xu
Summary: DHX9 overexpression in myelodysplastic syndromes (MDS) is associated with poor prognosis and high risk of acute myeloid leukemia (AML) transformation. DHX9 is essential for malignant proliferation of leukemia cells. Suppression of DHX9 increases cell apoptosis and sensitizes cells to chemotherapy. Additionally, DHX9 knockdown inactivates PI3K-AKT and ATR-Chk1 signaling, promotes R-loop accumulation, and leads to R-loop-mediated DNA damage.
Article
Oncology
Yasushige Aoyagi, Yoshihiro Hayashi, Yuka Harada, Kwangmin Choi, Natsumi Matsunuma, Daichi Sadato, Yuki Maemoto, Akihiro Ito, Shigeru Yanagi, Daniel T. Starczynowski, Hironori Harada
Summary: We demonstrated that excessive mitochondrial fragmentation is a fundamental pathobiological phenomenon that could trigger dysplasia formation and ineffective hematopoiesis in MDS. Our findings provide mechanistic insights into ineffective hematopoiesis and suggest dysregulated mitochondrial dynamics as a therapeutic target for treating MDS.
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.
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
David A. Sallman, Amy E. DeZern, Guillermo Garcia-Manero, David P. Steensma, Gail J. Roboz, Mikkael A. Sekeres, Thomas Cluzeau, Kendra L. Sweet, Amy McLemore, Kathy L. McGraw, John Puskas, Ling Zhang, Jiqiang Yao, Qianxing Mo, Lisa Nardelli, Najla H. Al Ali, Eric Padron, Greg Korbel, Eyal C. Attar, Hagop M. Kantarjian, Jeffrey E. Lancet, Pierre Fenaux, Alan F. List, Rami S. Komrokji
Summary: The combination treatment with eprenetapopt and azacitidine is well-tolerated and results in high rates of clinical response and molecular remissions in patients with TP53-mutant MDS and oligoblastic AML.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Naoyuki Kataoka, Eri Matsumoto, So Masaki
Summary: Pre-mRNA splicing is a crucial process for gene expression in higher eukaryotes, and mutations in splicing factors can lead to various human diseases, including MDS. Recent studies have shown that mutations in splicing factors play a driver role in human cancers, affecting about 50% of MDS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Aziz Nazha, Rami Komrokji, Manja Meggendorfer, Xuefei Jia, Nathan Radakovich, Jacob Shreve, C. Beau Hilton, Yasunubo Nagata, Betty K. Hamilton, Sudipto Mukherjee, Najla Al Ali, Wencke Walter, Stephan Hutter, Eric Padron, David Sallman, Teodora Kuzmanovic, Cassandra Kerr, Vera Adema, David P. Steensma, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero, Harry Erba, Claudia Haferlach, Jaroslaw P. Maciejewski, Torsten Haferlach, Mikkael A. Sekeres
Summary: This study developed a personalized prediction model for MDS patients using machine learning techniques and incorporating clinical and genomic data, which showed superior performance in predicting survival and leukemia transformation probabilities compared to established models. The model was validated in external cohorts, demonstrating its potential for dynamic and accurate prognostic predictions at different time points in a patient's disease course.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Hematology
Anthony M. Hunter, Rami S. Komrokji, Seongseok Yun, Najla Al Ali, Onyee Chan, Jinming Song, Mohammad Hussaini, Chetasi Talati, Kendra L. Sweet, Jeffrey E. Lancet, Eric Padron, Alan F. List, David A. Sallman
Summary: Baseline and sequential molecular profiling by NGS is valuable in identifying patients likely to benefit from HMAs in MDS treatment, particularly in cases with TP53 mutations. TET2 mutation and ASXL1 wild-type genotype are the strongest predictors of treatment response, while TP53 and EZH2 mutations are associated with inferior prognosis.
Article
Biochemistry & Molecular Biology
Hussein Awada, Carmelo Gurnari, Arda Durmaz, Hassan Awada, Simona Pagliuca, Valeria Visconte
Summary: Myelodysplastic syndromes (MDS) have variable clinical manifestations and prognoses. Prognostic systems have been developed to categorize MDS patients into different risk groups based on clinical factors and cytogenetic abnormalities. Incorporating molecular features into these systems may enhance their prognostic power. Machine learning algorithms can help develop precise prognostication models by integrating complex genomic interactions. This review highlights current prognostic models used in MDS and the latest achievements in machine learning-based research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Harrison K. Tsai, Christopher J. Gibson, H. Moses Murdock, Phani Davineni, Marian H. Harris, Eunice S. Wang, Lukasz P. Gondek, Annette S. Kim, Valentina Nardi, R. Coleman Lindsley
Summary: The study reveals the presence of complex secondary events in patients with KMT2A-PTD, which may be related to the occurrence and relapse of acute myeloid leukemia and myelodysplastic syndrome.
Review
Hematology
Eduard Schulz, Peter D. Aplan, Sylvie D. Freeman, Steven Z. Pavletic
Summary: Approximately 90% of MDS patients have oncogenic somatic mutations, and the genetic risk stratification and diagnosis criteria have improved. Monitoring MRD has been used in leukemias but not yet defined for MDS. This article discusses the evidence, challenges, and framework for integrating MRD into MDS treatment and clinical trials.
Article
Medicine, General & Internal
Huan Li, Fang Hu, Robert Peter Gale, Mikkael A. Sekeres, Yang Liang
Summary: Myelodysplastic syndromes (MDS) are a group of blood cancers characterized by dysregulated hematopoiesis and risk of transformation to acute myeloid leukemia. Prognostic systems can predict survival in MDS patients. Treatment goals differ for low-risk and high-risk MDS, with the aim to improve quality of life and prolong survival, respectively. Hematopoietic cell transplantation can cure MDS, but it is not widely used.
NATURE REVIEWS DISEASE PRIMERS
(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
Medicine, Research & Experimental
Kristen E. Schratz, Valeriya Gaysinskaya, Zoe L. Cosner, Emily A. DeBoy, Zhimin Xiang, Laura Kasch-Semenza, Liliana Florea, Pali D. Shah, Mary Armanios
Summary: The study revealed that patients with germline telomere maintenance defects exhibit diverse somatic adaptive mutations, which may alleviate the telomere crisis that promotes transformation to MDS/AML.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
