الفهرس 
Introduction
Microenvironment in MDSOnly 14 pages are availabe for public view
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Abstract
The myelodysplastic syndromes (MDS) encompass a series of hematologic conditions characterized by chronic cytopenias accompanied by abnormal cellular maturation. As a result, patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as progression to acute leukemia, which is often refractory to standard treatment. The precise incidence of de novo MDS is not known; however, estimates indicate that it exceeds the incidence of AML in the elderly. The risk of developing MDS increases with age. In one study, the annual incidence per 100,000 was estimated to be 0.5, 5.3, 15, 49, and 89 for individuals <50 years of age, 50 to 59, 60 to 69; 70 to 79; and >80 years, respectively. The median age in most series is ≥ 65 years, with a male predominance. Onset of the disease earlier than age 50 is unusual, with the exception of treatment- induced MDS. The majority of MDS have no known history of exposure to chemotherapy or radiation (de novo MDS). Possible aetiologies include benzene exposure, cigarette smoking and occupational exposure to solvents or agricultural chemicals. Some inherited haematological disorders, such as Fanconi’s anaemia, Diamond-Blackfan syndrome, congenital dyskeratosis and Shwachman-Diamond syndrome, are also associated with a high risk of MDS and AML. Other MDS appear as late toxicity of treatments for other malignancies, mainly with alkylating agents or topoisomerase II inhibitors. The diagnosis of MDS should be considered in any patient with unexplained cytopenias or monocytosis, especially elderly patients. Dysplastic cytological features of one or all hematopoietic lines seen in peripheral blood and bone marrow examination can aid in the diagnosis. Other etiologies of these changes, including nutritional deficiency, alcohol and drug use, medication side effects, toxic chemical exposure, prior treatment with antineoplastic agents or radiation, and HIV infection, should be excluded. The first MDS classification published by the French American-British (FAB) Cooperative Group in 1982, distinguished five subcategories: refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with an excess of blasts (RAEB), RAEB-in transformation (RAEB-T) and chronic myelomonocytic leukaemia (CMML). In 2001, the World Health Organization (WHO) modified the FAB classification by lowering the level of myeloblasts required for the diagnosis of AML to 20%, and placing CMML into a new category of myeloid neoplasms that have both myelodysplastic and myeloproliferative features. The WHO classification also recognizes multilineage dysplasia and isolated del (5q) syndrome as a distinctive category. In 2008, the classification was revised by adding additional changes and it now recognizes six categories of MDS. Altogether, neither the FAB nor the WHO classification system addresses the physiopathology of this clonal disease, and both remain focused on morphology, with little concession to molecular abnormalities. The course of disease may vary considerably; from a smoldering disease that may last for many years to a more aggressive appearance with severe bone marrow failure. In about 30% of cases transformed to AML. Increased apoptosis in bone marrow as well as immunological mechanisms may contribute to ineffective hematopoiesis. Cytogenetics aberrations may be found 50% of the case, and specific aberrations correlate with distinct prognosis. The genes that are critically involved in pathogenesis of MDS have remained elusive for a long time till application of novel technologies such as high resolution SNP-arrays. It is hoped that better understanding of the biological pathways that are disturbed in MDS will provide rationales for development of novel forms of therapy that will ameliorate the prognosis for these patients. A risk adapted treatment strategy is mandatory for conditions showing a so highly variable clinical course, and definition of the individual risk has been based so far on prognostic scoring system. A prognostic model that accounts for the WHO categories, cytogenetics and transfusion dependency has been developed. This WPSS is able to classify patients into 5 risk groups showing different survivals and probabilities of leukemic transformation. Several therapeutic tools have been proposed in last decades but only few survived the evidence based criteria efficacy. Patients with Very low risk: Watchful waiting strategy. Transfusion dependent patients with low risk WPSS risk can be treated with ESAs, transfusion dependent with del (5q) may respond to lenalidomide with cytogenetic remission and abolishment of transfusion requirements. A recent survival study showed that azacitidine increases OS in patients with higher risk MDS. But still the only treatment that can cure a patient with MDS is allogeneic stem cell transplantation, however, only a minority of all MDS patients are eligible and have a donor. MDS is a challenging disease with generally poor prognosis in adult patients. Survival is adversely affected by age, degree of cytopenia, presence of blasts, and abnormal karyotype.