Current Pharmaceutical Design - Volume 18, Issue 22, 2012

Myelodysplastic syndromes (MDS) are characterized by an ineffective hematopoiesis and functional abnormalities of hematopoietic lineages. Patients with MDS present with cytopenia(s) associated with morphological dysplasia and /or increase in number of blasts, and can progress to acute myeloid leukemia. The pathogenesis of MDS is exceedingly complex and involves the hematopoietic stem cells, bone marrow micr Read More

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic neoplasms characterized by ineffective hematopoiesis and a risk for progression to acute myeloid leukemia. A number of cytogenetic changes have been described that are characteristic to MDS and of clinical relevance; the specific gene targets of these alterations were largely unknown. On the other hand, over the past decade, technologies h Read More

MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs Read More

In recent years we have gained great insight into the molecular pathogenesis of the 5q- syndrome, the most distinct of all the myelodysplastic syndromes. It is now recognized that p53 activation, caused by haploinsufficiency for the ribosomal gene RPS14 (mapping to the commonly deleted region), is the probable cause of the erythroid defect in the 5q- syndrome. A mouse model of the human 5q- syndrome has been gener Read More

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases characterized by bone marrow failure, marrow dysplasia, and a tendency to evolve to acute leukemia. Pathophysiologically, low risk MDS are separated from the high risk category by an increased rate of apoptosis of the bone marrow cells which causes the morphological paradoxon of a peripheral cytopenia and hypercellular bone marro Read More

Unprecedented progress continues to be made in the treatment strategies for the myelodysplastic syndromes (MDS). This review provides an introduction to DNA methyltransferase inhibitors. These agents include 5-azacytidine (azacitidine; AZA) and 5-aza-2'- deoxycytidine (decitabine; DAC). In particular, AZA was shown for the first time to significantly prolong the life expectancy of high-risk MDS patients in international Read More

Lenalidomide is a second generation immunomodulatory agent (IMiD), which currently represents the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndrome (MDS) patients with deletion (5q). Lenalidomide has unique activity with a high transfusion independence rate observed in this subset of patients. In this article we summarize the clinical experience using lenalidomide for treatm Read More

Myelodysplastic syndromes (MDS) are a group of aquired hematopoietic disorders characterized by ineffective hematopoiesis, and increased risk of progression of acute myeloid leukemia. For a long period of time, the standard therapy for MDS was hematopoietic stem cell transplantation, however DNA methyltransferase inhibitors (DNMT inhibitors) including decitabine (DAC) and azacitidine (AZA), and lenalidomide, a deriv Read More

Hematopoietic cell transplantation (HCT) offers potentially curative therapy for patients with myelodysplastic syndromes (MDS). However, as most patients with MDS are in the 7th or 8th decade of life, only few of these were transplanted in the past, using high-dose conditioning regimens. The development of reduced-intensity conditioning has allowed to offer HCT also to older patients and those with clinically relevant comorbid Read More

The majority of patients with myelodysplastic syndromes (MDS) become transfusion-dependent during the course of disease and may thus develop transfusional iron overload. As a further contributor to iron overload there is increased absorption of dietary iron from the gut, as a consequence of ineffective erythropoiesis. Compared with thalassemia, it is less clear how frequent patients with MDS develop clinical complications of ir Read More

This paper will summarize the clinical features of transfusion-related acute lung injury (TRALI) before the experimental and clinical literature on the pathogenesis of TRALI is reviewed. Several mechanisms by which leukocyte antibodies induce TRALI have been unraveled. Significant advances have also been made in the field of recipient-related factors that contribute to the development of TRALI. In contrast, the pathomechani Read More

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion related morbidity and mortality. Immunemediated TRALI is caused by leucocyte and neutrophil antibodies in the transfused blood products that react with white blood cell antigens of the recipient, hereby inducing endothelial damage and lung injury. About two thirds of TRALI cases are thought to be immunemediated. Both Human Leucocyte Antibo Read More

Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary insufficiency induced by transfusion. TRALI is the leading cause of transfusion-related death, and is caused by the infusion of either anti-leukocyte antibodies in plasma containing blood products or neutrophil priming substances that accumulate during storage of cellular blood products. Among these neutrophil priming substances are bioactive Read More

Priming of polymorphonuclear leukocytes (PMNs) enhances their adhesion to endothelium, the release of their granule content and their production of reactive oxygen species. These effects are etiological in transfusion related acute lung injury (TRALI) and many clinically important mediators of TRALI prime PMNs. A priming activity that develops over time in stored blood products has been shown to be due to the accumulation of Read More

Transfusion-related acute lung injury (TRALI) is a major cause of morbidity and mortality in transfused hosts and like other causes of acute lung injury, there is no effective pharmacologic treatment. The pathophysiology of TRALI is still being defined, but neutrophils have a major role in the pathogenesis of both human and experimental studies. Recently, MHC antibody-based experimental TRALI models have revealed that pl Read More

Transfusion-related acute lung injury (TRALI) is a subcategory of acute lung injury (ALI). As such, there are many similarities between the syndromes, both clinically and pathophysiologically. Pulmonary changes in fibrin turnover have emerged as a hallmark of ALI, thereby initiating studies investigating the potential of therapeutic interventions aimed at ameliorating this so-called pulmonary coagulopathy. Enhanced c Read More

Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion-related mortality in most developed countries. Despite this fact, well-designed investigations on specific management strategies for TRALI are lacking. Indeed, current recommendations are primarily based on data extrapolated from trials of the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress Syndromes. The corner Read More

Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-associated death for nearly a decade. Recent TRALI mitigation strategies focused on reduction of leukocyte antibodies in high volume plasma products appear to be successful in reducing TRALI events and deaths, but additional preventive measures are needed. Future possibilities include, screening of donors for neutrophil antibodies, p Read More