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Telomere and Telomerase

18 Years
Not Enrolling
Acute Myeloid Leukemia

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Trial Information

Telomere and 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).

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

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Outcome Measure:

Identification and resolution of telomere dysfunction-induced focus (TIF) and normalization of telomerase activity

Outcome Description:

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.

Outcome Time Frame:

up to 24 weeks

Safety Issue:


Principal Investigator

Siddhartha Ganguly, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kansas


United States: Institutional Review Board

Study ID:




Start Date:

September 2010

Completion Date:

February 2011

Related Keywords:

  • Acute Myeloid Leukemia
  • AML
  • MDS
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



University of Kansas Medical Center, Westwood CampusKansas City, Kansas  66205