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Pathobiology : Journal of... 2019This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of... (Review)
Review
This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of patients with myelodysplastic syndrome (MDS). The revision was based on data accumulated since the 2008 WHO classification of MDS, much of which relates to new molecular genetic information about these neoplasms. The new information has led to some reorganization of the MDS disease categories, including a broadening of the subset of cases classified as MDS with ring sideroblasts, many of which have mutations in the spliceosome gene SF3B1. Other revisions have refined the definitions of some disease categories to improve disease risk stratification. The revised categories in the new classification ensure that MDS patients receive risk-adapted therapies based on the most recently available data.
Topics: Algorithms; Cytogenetics; Humans; Mutation; Myelodysplastic Syndromes; Myeloproliferative Disorders; Phosphoproteins; RNA Splicing Factors; World Health Organization
PubMed: 30041243
DOI: 10.1159/000489702 -
Clinics in Laboratory Medicine Dec 2023Myelodysplastic syndrome (MDS) in children is rare, accounting for < 5% of all childhood hematologic malignancies. With the advent of next-generation sequencing, the... (Review)
Review
Myelodysplastic syndrome (MDS) in children is rare, accounting for < 5% of all childhood hematologic malignancies. With the advent of next-generation sequencing, the etiology of many childhood MDS (cMDS) cases has been elucidated with the finding of predisposing germline mutations in one-quarter to one-third of cases; somatic mutations have also been identified, indicating that cMDS is different than adult MDS. Herein, cMDS classification schema, clinical presentation, laboratory values, bone marrow histology, differential diagnostic considerations, and the recent molecular findings of cMDS are described.
Topics: Adult; Child; Humans; Myelodysplastic Syndromes; Bone Marrow; Hematologic Neoplasms; Disease Susceptibility
PubMed: 37865508
DOI: 10.1016/j.cll.2023.06.005 -
Pathobiology : Journal of... 2019The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the... (Review)
Review
The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the Revised International Prognostic Scoring System (IPSS-R). In recent years, an increasing number of molecular aberrations have been discovered. They are already included in the classification (e.g., SF3B1) and, more importantly, have emerged as valuable markers for better classification, particularly for defining risk groups. Mutations in genes such as SF3B1 and IDH1/2 have already had an impact on targeted treatment approaches in MDS.
Topics: Biomarkers; Humans; Isocitrate Dehydrogenase; Mutation; Myelodysplastic Syndromes; Pathology, Molecular; Phosphoproteins; Prognosis; RNA Splicing Factors
PubMed: 29791902
DOI: 10.1159/000488712 -
International Journal of Molecular... Sep 2021Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and... (Review)
Review
Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS. Although these agents induce responses in up to 40-60% of patients, primary or secondary drug resistance is relatively common. To improve the treatment outcome, combinational therapies comprising HMA with targeted therapy or immunotherapy are being evaluated and are under continuous development. This review provides a comprehensive update of the molecular pathogenesis and immune-dysregulations involved in MDS, mechanisms of resistance to HMA, and strategies to overcome HMA resistance.
Topics: Antineoplastic Agents; Combined Modality Therapy; DNA Methylation; Humans; Immunotherapy; Molecular Targeted Therapy; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 34638574
DOI: 10.3390/ijms221910232 -
International Journal of Hematology Dec 2005
Topics: Antilymphocyte Serum; Cyclosporine; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Myelodysplastic Syndromes; Radiotherapy; Stem Cells
PubMed: 16533744
DOI: 10.1532/IJH97.05139 -
Georgian Medical News Jan 2023Given the difficulties of diagnosis, the absence of a typical clinical picture of myelodysplastic syndrome accompanied by cytopenia, a high risk of transformation into... (Review)
Review
Given the difficulties of diagnosis, the absence of a typical clinical picture of myelodysplastic syndrome accompanied by cytopenia, a high risk of transformation into acute myeloid leukemia, discussion of the formation, terminology, pathogenesis, classification, clinical course and principles of management of this group of tumor diseases is very relevant. The review article discusses the issues of terminology, pathogenesis, classification and diagnosis of myelodysplastic syndrome (MDS), as well as the principles of management of this category of patients. Due to the absence of a typical clinical picture of MDS, in order to exclude other diseases accompanied by cytopenia, not only routine hematological examination methods are necessary, but also a mandatory cytogenetic examination of the bone marrow. Treatment of patients with MDS should be individualized, taking into account risk group stratification, age and physical status. To improve the quality of life of patients with MDS, epigenetic therapy with azacitidine has an advantage. Myelodysplastic syndrome is an irreversible tumor process with a clear tendency to transform into acute leukemia. The diagnosis of MDS is always made with caution by excluding other diseases accompanied by cytopenia. To make a diagnosis, not only routine hematological examination methods are necessary, but also a mandatory cytogenetic study of the bone marrow. The management of patients with MDS is still an unresolved problem. The approach to the treatment of MDS should be individualized and based on the patient's risk group, age, and somatic status. Epigenetic therapy has an advantage when choosing management tactics for MDS in terms of improving the quality of life of patients.
Topics: Humans; Quality of Life; Prognosis; Myelodysplastic Syndromes; Leukemia; Azacitidine
PubMed: 36864802
DOI: No ID Found -
International Journal of Molecular... May 2021Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red... (Review)
Review
Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.
Topics: Animals; Erythropoiesis; Homeostasis; Humans; Iron; Iron Overload; Myelodysplastic Syndromes; Reactive Oxygen Species
PubMed: 34068996
DOI: 10.3390/ijms22105202 -
Current Opinion in Hematology Jul 1995Myelodysplastic syndrome continues to present a formidable clinical challenge. Despite considerable effort, no therapy apart from allogeneic bone marrow transplantation... (Review)
Review
Myelodysplastic syndrome continues to present a formidable clinical challenge. Despite considerable effort, no therapy apart from allogeneic bone marrow transplantation has been shown to prolong survival. Lack of effective therapy for myelodysplastic syndrome is of further concern given recent reports on the high incidence of myelodysplastic syndrome in patients undergoing intensive chemotherapy and radiation therapy for other malignancies. However, significant strides have been made in the past year toward understanding the molecular pathogenesis of some forms of myelodysplastic syndrome, as well as developing new approaches for therapy of myelodysplastic syndrome. This review highlights recent advances in the molecular genetics of myelodysplastic syndrome, including clonality analysis and identification of genes that are causally implicated in the pathogenesis of myelodysplastic syndrome; results from recent clinical trials for therapy of myelodysplastic syndrome using growth factors, chemotherapy or both; and recent literature on therapy-related myelodysplastic syndrome in intensively treated patients.
Topics: Antineoplastic Agents; Bone Marrow Transplantation; Chromosome Deletion; Clinical Trials as Topic; Hematopoietic Cell Growth Factors; Humans; Myelodysplastic Syndromes; Translocation, Genetic; Transplantation, Homologous
PubMed: 9372009
DOI: 10.1097/00062752-199502040-00008 -
Clinics in Laboratory Medicine Sep 2021Pediatric myelodysplastic syndromes (MDS) comprise less than 5% of childhood malignancies. Approximately 30% to 45% of pediatric MDS cases are associated with an... (Review)
Review
Pediatric myelodysplastic syndromes (MDS) comprise less than 5% of childhood malignancies. Approximately 30% to 45% of pediatric MDS cases are associated with an underlying genetic predisposition syndrome. A subset of patients present with MDS/acute myeloid leukemia (AML) following intensive chemotherapy for an unrelated malignancy. A definitive diagnosis of MDS can often only be rendered pending a comprehensive clinical and laboratory-based evaluation, which frequently includes ancillary testing in a reference laboratory. Clinical subtypes, the current diagnostic schema, and the results of more recently performed next-generation sequencing studies in pediatric MDS are discussed here.
Topics: Child; Genetic Predisposition to Disease; Humans; Myelodysplastic Syndromes
PubMed: 34304779
DOI: 10.1016/j.cll.2021.03.015 -
Best Practice & Research. Clinical... Dec 2017A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults... (Review)
Review
A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults are rapidly being identified. In recognition of the clinical impact of this emerging field, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have all added consideration of inherited predisposition to MDS/AML classification and management. Study of these disorders is providing unique insight into the biology of both sporadic and familial MDS/AML. International collaborative efforts to store germline tissue, document family histories, and pool data are essential to progress in diagnosing and treating both hereditary and sporadic forms of MDS/AML.
Topics: Genetic Diseases, Inborn; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
PubMed: 29156196
DOI: 10.1016/j.beha.2017.10.002