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Haematologica Aug 2016
Topics: Antimetabolites, Antineoplastic; Biomarkers, Tumor; Clinical Trials as Topic; Frustration; Humans; Myelodysplastic Syndromes
PubMed: 27478197
DOI: 10.3324/haematol.2016.142836 -
Annales de Biologie Clinique 2013Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included... (Review)
Review
Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included five categories basing on morphology and bone marrow blast count. Three criteria are taken into account: 1) the percentage of blasts in peripheral blood and bone marrow, 2) the percentage of ringed sideroblasts, and 3) the number of monocytes in peripheral blood. The World Health Organization classification (WHO 2001, 2008) modifies the FAB system by also taking cytogenetic characteristics and molecular biology into consideration. The last classification (WHO-2008) takes into account: 1) the number of peripheral cytopenia, 2) the percentage of blasts in peripheral blood and bone marrow, 3) the percentage of ringed sideroblasts, 4) the possible presence of Auer Rods, and 5) the detection of a cytogenetic abnormality (the isolated 5q deletion). The following subgroups are defined: refractory cytopenia with unilineage dysplasia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts, myelodysplastic syndrome unclassifiable and myelodysplastic syndrome with isolated del(5q).
Topics: Americas; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; France; Humans; Janus Kinase 2; Myelodysplastic Syndromes; Myeloproliferative Disorders; United Kingdom; World Health Organization
PubMed: 23587576
DOI: 10.1684/abc.2013.0804 -
Current Opinion in Hematology Mar 2021In the past decade, numerous studies analysing the genome and transcriptome of large cohorts of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients... (Review)
Review
PURPOSE OF REVIEW
In the past decade, numerous studies analysing the genome and transcriptome of large cohorts of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have substantially improved our knowledge of the genetic landscape of these diseases with the identification of heterogeneous constellations of germline and somatic mutations with prognostic and therapeutic relevance. However, inclusion of integrated genetic data into classification schema is still far from a reality. The purpose of this review is to summarize recent insights into the prevalence, pathogenic role, clonal architecture, prognostic impact and therapeutic management of genetic alterations across the spectrum of myeloid malignancies.
RECENT FINDINGS
Recent multiomic-studies, including analysis of genetic alterations at the single-cell resolution, have revealed a high heterogeneity of lesions in over 200 recurrently mutated genes affecting disease initiation, clonal evolution and clinical outcome. Artificial intelligence and specifically machine learning approaches have been applied to large cohorts of AML and MDS patients to define in an unbiased manner clinically meaningful disease patterns including, disease classification, prognostication and therapeutic vulnerability, paving the way for future use in clinical practice.
SUMMARY
Integration of genomic, transcriptomic, epigenomic and clinical data coupled to conventional and machine learning approaches will allow refined leukaemia classification and risk prognostication and will identify novel therapeutic targets for these still high-risk leukaemia subtypes.
Topics: Clinical Decision-Making; Clonal Evolution; Disease Management; Epigenomics; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Prognosis; Single-Cell Analysis; Treatment Outcome
PubMed: 33427759
DOI: 10.1097/MOH.0000000000000629 -
Clinical and Experimental Medicine Jul 2023Myelodysplastic syndrome (MDS) is a type of heterogeneous myeloid clonal disorder usually diagnosed based on a combination of multiple laboratory examinations, including...
BACKGROUND
Myelodysplastic syndrome (MDS) is a type of heterogeneous myeloid clonal disorder usually diagnosed based on a combination of multiple laboratory examinations, including analysis of peripheral blood cells, bone marrow cell morphology and cytogenetics. However, there is a certain difficulty in cases with no distinct changes in hematology and marrow cell morphology.
METHODS
We adopt flow cytometry to quantitatively analyze the immunophenotypic changes of marrow monocytes according to the surface antigens and their combinations at different differentiation stages, so as to study the changes of monocytes during differentiation in patients with bone marrow failure. In the meantime, the relationship between the immunophenotypic changes of marrow monocytes and IPSS-R score and prognosis of MDS patients was analyzed.
RESULTS
Our results demonstrated disorders of maturation and differentiation of monocytes in patients with MDS and clonal cytopenias of undetermined significance as compared to those with aplastic anemia and healthy individuals. In addition, the differentiation abnormality gradually increased with the disease progression. Furthermore, CD300e expression was found to show significant associations with the clinical stage and disease progression of MDS, and the progression-free survival and AML-free survival were much longer in MDS patients highly expressing CD300e on monocytes.
CONCLUSIONS
CCUS and MDS patients have disorders of differentiation and maturation of monocytes, which tends to be more critical with MDS progression or transforms to AML. Moreover, high CD300e expression has the potential to be a favorable prognostic marker for MDS. This study provides important insights to the role of monocyte immunotyping in the diagnosis, differentiation and prognosis of MDS.
Topics: Humans; Monocytes; Clinical Relevance; Myelodysplastic Syndromes; Prognosis; Disease Progression; Flow Cytometry
PubMed: 35916958
DOI: 10.1007/s10238-022-00856-7 -
The Western Journal of Medicine Aug 1989The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic and ineffective hematopoiesis and a varying risk... (Review)
Review
The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic and ineffective hematopoiesis and a varying risk of transformation to acute leukemia. Although the natural history of these syndromes is variable, several factors appear to be of prognostic importance, including the French-American-British classification, the karyotype, in vitro colony formation, and others. The pathogenesis of the myelodysplastic syndrome is not known, but recent evidence suggests that alterations of cellular oncogenes may be a causative factor. There is no standard therapy for myelodysplasia, and thus novel approaches to patient management are warranted.
Topics: Aged; Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 2672599
DOI: No ID Found -
Trends in Molecular Medicine Oct 2021Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders with limited treatment options. Anemia is a common symptom in MDS, and although... (Review)
Review
Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders with limited treatment options. Anemia is a common symptom in MDS, and although erythropoiesis-stimulating agents such as erythropoietin, lenalidomide, and luspatercept are available to treat anemia, many MDS patients do not respond to these first-line therapies. Therefore, alternative drug development strategies are needed to improve therapeutic efficacy. Splicing modulators to correct splicing-related defects have shown promising results in clinical trials. Targeting differentiation of early erythroid progenitors to increase the erythroid output in MDS is another novel approach, which has shown encouraging results at the pre-clinical stage. Together, these therapeutic strategies provide new avenues to target MDS symptoms untreatable previously.
Topics: Anemia; Humans; Myelodysplastic Syndromes
PubMed: 34257007
DOI: 10.1016/j.molmed.2021.06.013 -
Journal of Internal Medicine Jul 2019Next-generation sequencing (NGS) is rapidly changing the clinical care of patients with myelodysplastic syndrome (MDS). NGS can be used for various applications: (i) in... (Review)
Review
Next-generation sequencing (NGS) is rapidly changing the clinical care of patients with myelodysplastic syndrome (MDS). NGS can be used for various applications: (i) in the diagnostic process to discriminate between MDS and other diseases such as aplastic anaemia, myeloproliferative disorders and idiopathic cytopenias; (ii) for classification, for example, where the presence of SF3B1 mutation is one criterion for the ring sideroblast anaemia subgroups in the World Health Organization 2016 classification; (iii) for identification of patients suitable for targeted therapy (e.g. IDH1/2 inhibitors); (iv) for prognostication, for example, where specific mutations (e.g. TP53 and RUNX1) are associated with inferior prognosis, whereas others (e.g. SF3B1) are associated with superior prognosis; and (v) to monitor patients for progression or treatment failure. Most commonly, targeted sequencing for genes (normally 50-100 genes) reported to be recurrently mutated in myeloid disease is used. At present, NGS is rarely incorporated into clinical guidelines although an increasing number of studies have demonstrated the benefit of using NGS in the clinical management of MDS patients.
Topics: High-Throughput Nucleotide Sequencing; Humans; Myelodysplastic Syndromes; Sequence Analysis, DNA
PubMed: 30869816
DOI: 10.1111/joim.12893 -
Oncology (Williston Park, N.Y.) Sep 2002The bone marrow failure states, aplastic anemia and myelodysplastic syndrome, are characterized by reticulocytopenic anemia, with variable neutropenia and... (Review)
Review
The bone marrow failure states, aplastic anemia and myelodysplastic syndrome, are characterized by reticulocytopenic anemia, with variable neutropenia and thrombocytopenia. The bone marrow biopsy is very hypocellular in aplastic anemia, but it is usually hypercellular in myelodysplastic syndrome. Marrow cytogenetic abnormalities are present in approximately half of myelodysplastic syndrome patients but are absent in aplastic anemia. Allogeneic bone marrow transplantation is the treatment of choice for young patients with severe aplastic anemia. Immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine is used when transplantation is not the initial therapeutic choice; it induces responses in 65% to 80% of patients. Treatment of myelodysplastic syndrome is dependent upon risk classification, and patient age and performance status. Allogeneic stem cell transplantation should be considered for younger myelodysplastic syndrome patients. An acute myelogenous leukemia (AML) type of induction chemotherapy may benefit high-risk patients with a good performance status for whom allogeneic transplantation is not an option. Patients achieving a complete remission to induction chemotherapy may be considered for autologous stem cell transplantation. However, aggressive therapy is an option for only a minority of myelodysplastic syndrome patients; most receive supportive care. Anemia, and its related symptoms, is the principal problem for most myelodysplastic syndrome patients. Erythropoietin administration ameliorates anemia in a minority of myelodysplastic syndrome patients. A wide variety of novel experimental approaches including immunosuppressive therapy, angiogenesis inhibitors, platelet growth factors, and demethylating agents are now under investigation for myelodysplastic syndrome.
Topics: Anemia, Aplastic; Humans; Myelodysplastic Syndromes
PubMed: 12380966
DOI: No ID Found -
Hematology/oncology Clinics of North... Apr 2020Myelodysplastic syndromes (MDSs) are a heterogeneous group of marrow failure disorders that primarily affect older persons but also occur at a lower frequency in... (Review)
Review
Myelodysplastic syndromes (MDSs) are a heterogeneous group of marrow failure disorders that primarily affect older persons but also occur at a lower frequency in children and young adults. There is increasing recognition of an inherited predisposition to MDS as well as other myeloid malignancies for patients of all ages. Germline predisposition to MDS can occur as part of a syndrome or sporadic disease. The timely diagnosis of an underlying genetic predisposition in the setting of MDS is important. This article delineates germline genetic causes of MDS and provides a scaffold for the diagnosis and management of patients in this context.
Topics: Biomarkers; Clonal Evolution; Disease Management; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Hematopoiesis; Humans; Molecular Diagnostic Techniques; Myelodysplastic Syndromes
PubMed: 32089214
DOI: 10.1016/j.hoc.2019.10.002 -
Hematology. American Society of... Dec 2017Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The... (Review)
Review
Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation.
Topics: Bone Marrow; Hematopoiesis; Humans; Mutation; Myelodysplastic Syndromes
PubMed: 29222292
DOI: 10.1182/asheducation-2017.1.447