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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: 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

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center, Westwood Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification and resolution of telomere dysfunction-induced focus (TIF) and normalization of telomerase activity	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.	up to 24 weeks

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Siddhartha Ganguly, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: August 3, 2010
• First Submitted That Met QC Criteria: August 4, 2010
• First Posted (Estimate): August 6, 2010

Study Record Updates

• Last Update Posted (Estimate): January 10, 2017
• Last Update Submitted That Met QC Criteria: January 6, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: AML; MDS
• Other Study ID Numbers: 12016