Telomere and Telomerase

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01176422
Recruitment Status : Withdrawn (lack of resources; no patient enrollment)
First Posted : August 6, 2010
Last Update Posted : January 10, 2017
Information provided by (Responsible Party):
University of Kansas Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment
Acute Myeloid Leukemia Genetic: Blood sample

Detailed Description:

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).

Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Telomere and Telomerase
Study Start Date : September 2010
Actual Primary Completion Date : February 2011
Actual Study Completion Date : February 2011

Group/Cohort Intervention/treatment
advanced Myelodysplastic Syndrome or acute myeloid leukemia
advanced MDS and AML with/without associated cytogenetic abnormality
Genetic: Blood sample
Blood samples will be collected before and after treatment completion.

Primary Outcome Measures :
  1. Identification and resolution of telomere dysfunction-induced focus (TIF) and normalization of telomerase activity [ Time Frame: up to 24 weeks ]

    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.

Biospecimen Retention:   Samples With DNA
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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients will be selected from the BMT/Hematology clinic in the Cancer Center.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01176422

United States, Kansas
University of Kansas Medical Center, Westwood Campus
Westwood, Kansas, United States, 66205
Sponsors and Collaborators
University of Kansas Medical Center
Principal Investigator: Siddhartha Ganguly, MD University of Kansas Medical Center

Responsible Party: University of Kansas Medical Center Identifier: NCT01176422     History of Changes
Other Study ID Numbers: 12016
First Posted: August 6, 2010    Key Record Dates
Last Update Posted: January 10, 2017
Last Verified: January 2017

Keywords provided by University of Kansas Medical Center:

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type