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Thrombocytopenia is a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) [1]. Ineffective hematopoiesis and infiltration of the...

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and risk of evolution to acute myeloid leukemia (AML) [1]. Presentation varies from mild cytopenia to profound symptom...

To the Editor,The myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic conditions characterized by dysplastic changes and ineffective hematopoiesis [1]. Almost all patients with...

Myelodysplastic syndromes (MDS) represent a wide range of malignant hematological stem cell disorders characterized by ineffective hematopoiesis with dysplasia, peripheral cytopenias, and a propens...

Myelodysplastic syndrome (MDS) is a heterogeneous clonal myeloid neoplasm of ineffective hematopoiesis, dysplasia and an increased risk of progression to acute myeloid leukemia (AML) [1]. Although ...

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and an increased risk of transformation to acute myeloid leukemia (A...

Myelodysplastic syndromes (MDS) are a group of clonal marrow stem cell disorders characterized by progressive peripheral cytopenias and ineffective hematopoiesis with an associated risk of progress...

Myelofibrosis (MF) is characterized by progressive bone marrow fibrosis, ineffective hematopoiesis and extramedullary hematopoiesis with splenomegaly. The primary symptoms resulting from peripheral...

Myelodysplastic syndromes (MDS) are a heterogeneous group of malignant clonal disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia (AML) [1]. Recep...

Myelodysplastic syndrome (MDS) is an enigmatic disorder characterized by ineffective hematopoiesis and dysplastic morphology of blood cells. The clinical course of MDS consists of distinct stages, with early stages often progressing to advanced ones or to acute myeloid leukemia (AML). Little is known of the molecular pathogenesis of MDS or of the mechanism of its stage progression. DNA micro-array analysis, which allows simultaneous monitoring of the expression levels of tens of thousands of genes, has the potential to provide insight into the pathophysiology of MDS. Several studies have applied this new technology to compare gene expression profiles either between MDS and the healthy condition, among the different stages of MDS or between MDS-derived AML and de novo AML. Selection of an appropriate hematopoietic fraction is important for such studies, which to date have been performed with differentiated granulocytes, CD34+ progenitors and CD133+ immature cells. These studies have revealed that each stage of MDS has its own 'molecular signature', indicating the feasibility of differential diagnosis of MDS based on gene expression profile. They have also demonstrated that the current clinical diagnosis of MDS results in the misclassification of patients with regard to these molecular signatures.

Excess apoptosis leading to ineffective hematopoiesis is a common feature of myelodysplastic syndrome (MDS). CD178 (Fas ligand/APO-1 ligand) and CD137 ligand (CD137L), 2 molecules involved in the regulation of apoptosis, have previously been found in sera of patients with malignancies and have been hypothesized to participate in the pathogenesis of various diseases. We analyzed sera of patients with MDS and found that while time to progression of MDS correlated with the IPSS score there was no correlation of CD137L or CD178 serum levels with this score or with karyotype, bone marrow blast count or cytopenia. However, when cut-off-values for significant differentiation between cases with higher/lower levels of these molecules were determined we found that high levels of soluble CD137L (sCD137L) and low serum levels of soluble CD178 (sCD178) correlate with statistical significance to rapid progression of disease as estimated by log-rank-test. Conversely, low levels of sCD137L and high levels of sCD178 correlate significantly with prolongation of time to progression of disease. Our results indicate that serum levels of sCD137L and sCD178 represent valuable novel indicators for prognosis and disease progression and may be a useful parameter for treatment decisions in patients with MDS.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

The myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematological disorders, characterised by ineffective hematopoiesis [1]. Anemia in low grade MDS [refractory anemia (RA), refr...

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of hematopoiesis involving hyperproliferative and ineffective hematopoiesis associated with morphologic evidence of marrow cell dysplasia resulting in refractory cytopenia(s), and an increased risk of transformation into acute myeloblastic leukemia (AML). The administration of colony-stimulating factor(s) (CSFs) to patients with MDS increased blood neutrophil concentrations, in most patients, and was also expected to be beneficial and to prevent infections. However, the progression to AML during the treatment with CSFs was suspected in some patients. Therefore, extensive in vitro studies were expected to lead to the establishment of criteria for selection of patients who are likely to benefit from CSF's as well as to establish the overall value of the different types of CSFs therapy. For this purpose, in vitro colony assays provide an excellent tool for investigating the biologic characteristics of MDS progenitor cells. However, conditions of the culture must be such that each progenitor can express its full potential for proliferation and differentiation. Because of the above, MDS progenitor cells cannot be used because they carry an impairment in proliferation and differentiation. To address this problem, one needs to know how many cells are being handled and the maximum numbers of colonies and clusters expected. CD34, a stem cell phenotype, is at present one of the best markers of progenitor cells, and can be used for purposes of purification. Using a defined number of CD34+ cells, it was feasible to make direct investigations on MDS progenitor cells. In this review the properties of MDS progenitor cells are described, in association with proliferation and differentiation, with special emphasis on the phenotypic subpopulations of MDS CD34+ cells.