The Role of Erythropoietin in Myelodysplastic Syndrome

NCT ID: NCT00723112

Last Updated: 2010-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

8 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-02-28

Study Completion Date

2010-10-31

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.

Conditions

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Myelodysplastic Syndrome

Keywords

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Myelodysplastic Syndrome Erythropoiesis Ineffective Hematopoiesis Erythroid Progenitors Dyserythropoiesis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Affected Group

Adult subjects with the diagnosis of MDS based on the French-American-British classification system.

No interventions assigned to this group

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

No interventions assigned to this group

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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University of Utah

Principal Investigators

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Josef T Prchal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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University of Utah

Salt Lake City, Utah, United States

Site Status

VA Salt Lake City Health Care System

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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Aul C, Arning M, Runde V, Schneider W. Serum erythropoietin concentrations in patients with myelodysplastic syndromes. Leuk Res. 1991;15(7):571-5. doi: 10.1016/0145-2126(91)90025-o.

Reference Type BACKGROUND
PMID: 1861540 (View on PubMed)

Stasi R, Brunetti M, Terzoli E, Abruzzese E, Amadori S. Once-weekly dosing of recombinant human erythropoietin alpha in patients with myelodysplastic syndromes unresponsive to conventional dosing. Ann Oncol. 2004 Nov;15(11):1684-90. doi: 10.1093/annonc/mdh428.

Reference Type BACKGROUND
PMID: 15520072 (View on PubMed)

Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarre MC, Damaj G, Giraudier S, Guerci A, Laurent G, Dombret H, Chomienne C, Ribrag V, Stamatoullas A, Marie JP, Vekhoff A, Maloisel F, Navarro R, Dreyfus F, Fenaux P. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004 Jul 15;104(2):321-7. doi: 10.1182/blood-2003-07-2252. Epub 2004 Mar 30.

Reference Type BACKGROUND
PMID: 15054036 (View on PubMed)

Solignac M; European Hematology Association. [Epoetin beta, new strategies to optimise the management of anaemia in cancer patients]. Presse Med. 2003 Sep 13;32(29):1385-8. No abstract available. French.

Reference Type BACKGROUND
PMID: 14534506 (View on PubMed)

Fontenay-Roupie M, Bouscary D, Guesnu M, Picard F, Melle J, Lacombe C, Gisselbrecht S, Mayeux P, Dreyfus F. Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br J Haematol. 1999 Aug;106(2):464-73. doi: 10.1046/j.1365-2141.1999.01539.x.

Reference Type BACKGROUND
PMID: 10460607 (View on PubMed)

Takeshita A, Shinjo K, Naito K, Ohnishi K, Higuchi M, Ohno R. Erythropoietin receptor in myelodysplastic syndrome and leukemia. Leuk Lymphoma. 2002 Feb;43(2):261-4. doi: 10.1080/10428190290006026.

Reference Type BACKGROUND
PMID: 11999556 (View on PubMed)

Shinjo K, Takeshita A, Higuchi M, Ohnishi K, Ohno R. Erythropoietin receptor expression on human bone marrow erythroid precursor cells by a newly-devised quantitative flow-cytometric assay. Br J Haematol. 1997 Mar;96(3):551-8. doi: 10.1046/j.1365-2141.1997.d01-2071.x.

Reference Type BACKGROUND
PMID: 9054663 (View on PubMed)

McMullin MF, Percy MJ. Erythropoietin receptor and hematological disease. Am J Hematol. 1999 Jan;60(1):55-60. doi: 10.1002/(sici)1096-8652(199901)60:13.0.co;2-v.

Reference Type BACKGROUND
PMID: 9883806 (View on PubMed)

Kralovics R, Sokol L, Broxson EH Jr, Prchal JT. The erythropoietin receptor gene is not linked with the polycythemia phenotype in a family with autosomal dominant primary polycythemia. Proc Assoc Am Physicians. 1997 Nov;109(6):580-5.

Reference Type BACKGROUND
PMID: 9394420 (View on PubMed)

Kralovics R, Indrak K, Stopka T, Berman BW, Prchal JF, Prchal JT. Two new EPO receptor mutations: truncated EPO receptors are most frequently associated with primary familial and congenital polycythemias. Blood. 1997 Sep 1;90(5):2057-61.

Reference Type BACKGROUND
PMID: 9292543 (View on PubMed)

Stopka T, Zivny JH, Stopkova P, Prchal JF, Prchal JT. Human hematopoietic progenitors express erythropoietin. Blood. 1998 May 15;91(10):3766-72.

Reference Type BACKGROUND
PMID: 9573013 (View on PubMed)

Sato TN. A new role of lipid receptors in vascular and cardiac morphogenesis. J Clin Invest. 2000 Oct;106(8):939-40. doi: 10.1172/JCI11304. No abstract available.

Reference Type BACKGROUND
PMID: 11032853 (View on PubMed)

Other Identifiers

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DK007115-31

Identifier Type: -

Identifier Source: secondary_id

20716

Identifier Type: -

Identifier Source: org_study_id