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Telomere and Telomerase

This study has been terminated.
(lack of resources; no patient enrollment)
Sponsor:
Information provided by (Responsible Party):
University of Kansas
ClinicalTrials.gov Identifier:
NCT01176422
First received: August 3, 2010
Last updated: October 14, 2011
Last verified: October 2011

August 3, 2010
October 14, 2011
September 2010
February 2011   (final data collection date for primary outcome measure)
Identification and resolution of telomere dysfunction-induced focus (TIF) and normalization of telomerase activity [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]

Advancing myelodysplasia is associated with progressive telomere attrition and clonal chromosomal evolution. Based on this hypothesis, we expect to see identification of TIF by immunostaining and increase in Telomerase activity in peripheral blood granulocytes of patients with advanced Myelodysplastic Syndrome (MDS) and acute myeloid leukemia.

We also expect to see resolution of TIF and normalization of telomerase activity upon treatment.

Identification and resolution of telomere dysfunction-induced focus (TIF) and normalization of telomerase activity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Advancing myelodysplasia is associated with progressive telomere attrition and clonal chromosomal evolution. Based on this hypothesis, we expect to see identification of TIF by immunostaining and increase in Telomerase activity in peripheral blood granulocytes of patients with advanced Myelodysplastic Syndrome (MDS) and acute myeloid leukemia.

We also expect to see resolution of TIF and normalization of telomerase activity upon treatment.

Complete list of historical versions of study NCT01176422 on ClinicalTrials.gov Archive Site
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Telomere and Telomerase
Telomere and Telomerase

Researchers hope to determine if the DNA is shortened in your body and determine if there is an increase in the protein that shortens DNA called telomerase.

A telomere is a region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction. Telomeres can be viewed as the tips on the ends of shoelaces that keep them from unraveling. Telomeres compensate for incomplete semi-conservative DNA replication at chromosomal ends. In absence of a reparative process, DNA sequences would be lost in every replicative phase until they reached a critical level, at which point cell division would stop.

Loss of telomeres leads to chromosome end-to-end fusion, chromosome re-arrangements, and genome instability.

Telomerase is a "ribonucleoprotein complex" composed of a protein component and an RNA primer sequence which acts to protect the terminal ends of chromosomes. Telomerase is the natural enzyme which promotes telomere repair. It is however not active in most cells. It certainly is active though in stem cells, germ cells, hair follicles and in 90 percent of cancer cells. Telomerase functions by adding bases to the ends of the telomeres. As a result of this telomerase activity, these cells seem to possess a kind of immortality.

Progressive shortening or attrition of telomere length with consequent genomic instability leading to cancer has been described in various hematological malignancies including acute and chronic myeloid leukemia.

Reduced telomere length has been documented in patients with the progressive BM failure syndrome called Dyskeratosis Congenita. Abnormalities in these patients include skin pigmentation, nail dystrophy and leukoplakia. Mutations in the telomere maintenance mechanism have been implicated in the pathogenesis of this heterogeneous condition.

Myelodysplastic syndrome is an acquired clonal stem cell disorder characterized by in-effective hematopoiesis, increased intra-medullary apoptosis and peripheral cytopenia. A number of such patients will eventually develop worsening cytopenia evolving into acute myeloid leukemia. A number of studies have investigated telomerase activity and telomere length in patients with MDS and AML. Telomere shortening was significantly more pronounced in patients with cytogenetic alterations as compared to patients with normal karyotypes.

Genomic instability develops with progressive telomere shortening. The Telomere attrition related genome instability is a stress that leads to up-regulation of specified DNA damage foci. These telomere-associated DNA damage points are often called as Telomere Dysfunction-Induced Focus (TIF).

Observational
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:

Two teaspoons of blood will be collected - one teaspoon before subject begins treatment for disease and one teaspoon will be collected when subject completes treatment.

Probability Sample

Patients will be selected from the BMT/Hematology clinic in the Cancer Center.

Acute Myeloid Leukemia
Genetic: Blood sample
Blood samples will be collected before and after treatment completion.
advanced Myelodysplastic Syndrome or acute myeloid leukemia
advanced MDS and AML with/without associated cytogenetic abnormality
Intervention: Genetic: Blood sample
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
0
February 2011
February 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of advanced Myelodysplastic Syndrome (MDS) or acute myeloid leukemia
  • must be 18 years of age
  • must be able to give written informed consent
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01176422
12016
No
University of Kansas
University of Kansas
Not Provided
Principal Investigator: Siddhartha Ganguly, MD University of Kansas
University of Kansas
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP