Mechanisms underlying the heterogeneity of myelodysplastic syndromes

• In myelodysplastic syndromes, the disease-initiating cell is a rare hematopoietic stem cell which transmits the genetic abnormalities to its myeloid and lymphoid progeny.• The heterogeneity of MDS phenotypes is related to the diversity of genetic, the various combinations and order of mutation s in cooperating genes, and the variegation of clonal hematopoietic hierarchy.• A mutation in granulo-monocytic progenitor may the transformation into acute myeloid leukemia.
Source: Experimental Hematology - Category: Hematology Authors: Tags: Review Source Type: research

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Conclusion: The "Clo-Baltimore regimen" is safe and feasible and provides good survivals for patients with myeloid malignancies and haplo-donors. Methods: Here, we report a variant of the Baltimore regimen, where 1) fludarabine was replaced by clofarabine, 2) bone marrow was replaced by peripheral blood stem cells, and 3) tacrolimus was replaced by cyclosporine, in a "Clo-Baltimore regimen". PMID: 30323896 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Purpose of review Myelodysplastic syndromes (MDSs) are rare disorders in children, showing peculiar clinical manifestations and biological features. This review will summarize biological, genetic and clinical features of childhood MDS and will provide an update of the algorithm of treatment of the different disease variants. Recent findings The most recent classification of MDS includes refractory cytopenia of childhood (RCC), advanced and therapy-related MDS. Importantly, in children, these clonal hematopoietic disorders may be often associated with inherited bone marrow failure syndromes, this representing a challen...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research
Purpose of review The monitoring of minimal residual disease (MRD) has important clinical implications in both the pre and postallogeneic stem cell transplant (SCT) setting in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Next-generation sequencing (NGS) is a rapidly improving technology whose application to the monitoring of MRD is an active area of research. We aim to describe existing methods of MRD in AML and MDS, with a focus on the utility of NGS in patients undergoing SCT. Recent findings Flow cytometry and quantitative PCR have been recommended by the European Leukemia Net as the preferred m...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research
The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders that lead to bone marrow failure and an increased risk of progression to acute myelogenous leukemia (AML). As many as one in 1000 Canadians over the age of 65 years may be affected [1], and data from the Surveillance, Epidemiology, and End Results (SEER) Program in the United States (US) indicates an MDS incidence up to 4.5 per 100,000 per year, or 10,000 or more new MDS diagnoses yearly [2]. The incidence of MDS increases with age, with 0.5, 5.3, 15, 49, and 89 cases per 100,000 in the age groups
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
Patients with myelodysplastic syndromes (MDS) show heterogeneous clinical features with variation in ineffective hematopoiesis, morphological dysplasia, and progression to acute myeloid leukemia (AML) [1]. MDS arises from abnormal hematopoietic stem cells, with detectable somatic mutations in virtually all patients [2,3], and recent studies also showed that germline mutations are found in a portion of MDS [4,5]. These results clearly demonstrate that the genomic status is highly influential on clinical features of MDS [3].
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Abstract Myelodysplastic syndromes are hematologic malignancies with few treatment options and a propensity to transform to acute myeloid leukemia. In this issue of Cell Stem Cell, Sun et al. (2018) report that low SIRT1 levels in myelodysplastic stem cells contribute to aberrant self-renewal through enabling hyperacetylation and reduced activity of TET2. PMID: 30193128 [PubMed - in process]
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
A diagnosis of myelodysplastic syndrome (MDS), i.e. a cancerous disease with a variable risk of evolution into acute myeloid leukaemia [1] can trigger different emotions, particularly, psychological distress [2], as MDS can potentially be a life-threatening disease without any curative treatment except stem-cell transplant, which is not applicable for most patients [3]. Among lower-risk patients watchful waiting or symptomatic treatment might also generate distress because of the lack of MDS-focused treatment.
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
CONCLUSIONS: We found no evidence for a difference between participants receiving ATRA in addition to chemotherapy or chemotherapy only for the outcome OS. Regarding DFS, CRR and on-study mortality, there is probably no evidence for a difference between treatment groups. Currently, it seems the risk of adverse events are comparable to chemotherapy only.As quality of life has not been evaluated in any of the included trials, further research is needed to clarify the effect of ATRA on quality of life. PMID: 30080246 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
z M, Alousi A, Couriel D, Pidala J, Arora M, Cutler C Abstract Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in Consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graf...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
AbstractPurpose of ReviewApoptosis results from the interaction between pro- and anti-apoptotic proteins, mediated by BCL-2 homology 3 (BH3) proteins. B cell lymphoma-2 (BCL-2) is an inhibitor of apoptosis which stabilizes the mitochondria, resulting in the prevention of activation of the pro-apoptotic proteins. In addition, BCL-2 is overexpressed in the leukemic stem cell (LSC) population, and its inhibition may lead to selective LSC eradication. Herein, we will discuss the mechanism and rationale of BCL-2 inhibition in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an overview of the selective BCL-...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
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