The Role of Erythropoietin in Myelodysplastic Syndrome - Full Text View

Purpose

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

Condition
Myelodysplastic Syndrome

Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Prospective
Official Title:	The Role of Erythropoietin in Myelodysplastic Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Myelodysplastic Syndromes

Drug Information available for: Erythropoietin Epoetin Alfa

U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome Measures:

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. [ Time Frame: After Samples are obtained ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Enrollment:	8
Study Start Date:	February 2007
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts
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

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Subjects diagnosed with myelodysplastic syndrome

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723112

Locations

United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
VA Salt Lake City Health Care System
Salt lake City, Utah, United States, 84148

Sponsors and Collaborators

University of Utah

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Josef T Prchal, MD

University of Utah

More Information

Publications:

Aul C, Arning M, Runde V, Schneider W. Serum erythropoietin concentrations in patients with myelodysplastic syndromes. Leuk Res. 1991;15(7):571-5.

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.

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. Epub 2004 Mar 30.

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. French. No abstract available.

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.

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. Review.

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.

McMullin MF, Percy MJ. Erythropoietin receptor and hematological disease. Am J Hematol. 1999 Jan;60(1):55-60. Review.

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.

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.

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

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

Responsible Party:	Josef T. Prchal, MD, University of Utah
ClinicalTrials.gov Identifier:	NCT00723112 History of Changes
Other Study ID Numbers:	20716, DK007115-31
Study First Received:	July 24, 2008
Last Updated:	November 22, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Utah:

Myelodysplastic Syndrome
Erythropoiesis
Ineffective Hematopoiesis
Erythroid Progenitors
Dyserythropoiesis

Additional relevant MeSH terms:

Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms

Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013