The Role of Erythropoietin in Myelodysplastic Syndrome

• Analyze intrinsic erythroid Epo expression to determine whether it differs between normal controls and patients with MDS. [ Time Frame: After samples are obtained ] [ Designated as safety issue: No ]
• Perform a microarray analysis of genes associated with Epo signal transduction to determine if MDS patients have abnormal expression of signal transduction proteins. [ Time Frame: After samples are obtained ] [ Designated as safety issue: No ]
• Determine how often and what percent clonality occurs in MDS patients and try to predict who has early MDS by clonality testing. [ Time Frame: After samples from female patients have been obtained ] [ Designated as safety issue: No ]

• Analyze intrinsic erythroid Epo expression to determine whether it differs between normal controls and patients with MDS. [ Time Frame: After samples are obtained ] [ Designated as safety issue: No ]
• Perform a microarray analysis of genes associated with Epo signal transduction to determine if MDS patients have abnormal expression of signal transduction proteins. [ Time Frame: After samples are obtained ] [ Designated as safety issue: No ]

The purpose of the study is to elucidate the causative molecular events responsible for the abnormal erythropoiesis in MDS.

Myelodysplastic syndromes are a heterogeneous group of disorders characterized by clonal expansion of hematopoietic stem cells and ineffective hematopoiesis. Although all 3 cell lineages in myeloid hematopoiesis can be involved, the erythroid dysplasia and ineffective erythropoiesis of MDS are usually the most severe, and often precede the development of other bone marrow lineage defects.

In normal erythropoiesis, erythroid progenitors differentiate and proliferate in response to stimulation by erythropoietin (Epo). Epo binds to its receptor, EpoR, constitutively expressed at the surface of committed erythroid progenitors and induces homodimerization. This study is designed to evaluate the EpoR cDNA sequence and its level of expression in the clonal erythroid progenitors of MDS patients (in cells stratified for the same degree of erythroid maturation) to determine whether mutations in the EpoR may be responsible for an aberrant Epo signal transduction in MDS. As well as analyze intrinsic erythroid Epo expression to determine whether it differs between normal controls and patients with MDS and perform a microarray analysis of genes associated with Epo signal transduction to determine if MDS patients have abnormal expression of signal transduction proteins.

Subjects diagnosed with myelodysplastic syndrome

• Affected Group
  Adult subjects with the diagnosis of MDS based on the French-American-British classification system.
• Healthy Controls
  Control subjects will be selected using frequency matching on gender and age by decade. That is for each MDS patient a healthy volunteer of the same gender and decade (50-59, 60-69, 70-79, etc) will be selected

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Inclusion Criteria:

• Adult subjects greater than 18 years of age
• Diagnosis of MDS based on the French-American-British classification system (including secondary causes of MDS)

Exclusion Criteria:

• Subjects not meeting the criteria listed above