The Role of Erythropoietin in Myelodysplastic Syndrome

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

Detailed Description
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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.

Official Title
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The Role of Erythropoietin in Myelodysplastic Syndrome

Conditions
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Myelodysplastic Syndrome

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Affected Group<br>Adult subjects with the diagnosis of MDS based on the French-American-British classification system. | |
| Healthy Controls<br>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 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the EpoR cDNA sequence and its level of expression in the clonal erythroid progenitors of MDS patients to determine whether mutations in the EpoR may be responsible for an aberrant Epo signal transduction in MDS. |  | After Samples are obtained | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analyze intrinsic erythroid Epo expression to determine whether it differs between normal controls and patients with MDS. |  | After samples are obtained | 
| Perform a microarray analysis of genes associated with Epo signal transduction to determine if MDS patients have abnormal expression of signal transduction proteins. |  | After samples are obtained | 
| Determine how often and what percent clonality occurs in MDS patients and try to predict who has early MDS by clonality testing. |  | After samples from female patients have been obtained | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndrome, Erythropoiesis, Ineffective Hematopoiesis, Erythroid Progenitors, Dyserythropoiesis