The Role of Erythropoietin in Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

Official title:

The Role of Erythropoietin in Myelodysplastic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00723112
• Other study ID #: 20716
• Secondary ID: DK007115-31
• Status: Completed
• Phase: N/A
• First received: July 24, 2008
• Last updated: November 22, 2010
• Start date: February 2007
• Est. completion date: October 2010

Study information

• Verified date: November 2010
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah
United States	VA Salt Lake City Health Care System	Salt lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (12)

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

Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarré 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

Sato TN. A new role of lipid receptors in vascular and cardiac morphogenesis. J Clin Invest. 2000 Oct;106(8):939-40. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Analyze intrinsic erythroid Epo expression to determine whether it differs between normal controls and patients with MDS.		After samples are obtained	No
Secondary	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	No
Secondary	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	No