Molecular Evaluation of Telomere length in patients with mantle cell lymphoma (MCL)

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 21 de marzo del 2007

Share article


Presenter: Cottliar, A.
Presenter's Affiliation: Academia Nacional de Medicina, Argentina
Type of Session: Scientific

Background

  • Mantle cell lymphoma (MCL) is a rare (6% of NHL), but aggressive NHL with median survival of 3-4 years. MCL is genetically characterized by the t(11;14)(q13;q32) translocation (Cyclin D1:IgH) and up-regulation of Cyclin D1 gene.
  • Telomeres are repeated DNA sequences at the ends of chromosomes, which play a key role in maintaining chromosomal stability. Telomere shortening is associated with genomic changes involved in neoplastic transformation.
  • This study was conducted to study the molecular telomere length in patients with MCL and to correlate this with other genetic findings.

Materials and Methods
Patients:

  • 18 patients with MCL
  • 14 males
  • Mean age: 58 years (30-83 years)
  • samples were collected from bone marrow (13), lymph nodes (4), and peripheral blood (4)
Laboratory Studies:
  • Telomere length was studied using the telomere restriction fragment (TRF) assay on DNA samples in both patients and controls.
  • Cytogenetic studies, fluorescence in situ hybridization (FISH) and molecular analysis (by semi-nested PCR) to detect the Cyclin D1/IgH rearrangement.

Results

  • The TRF mean value was significantly shorter in patients (4.33±0.72Kb) vs. controls (8.5±0.5Kb) (p<0.001).
  • 10 patients had only one TRF peak (4.37±0.68Kb). The remaining ones showed two TRF peaks, the smaller representing the tumor component (4.12±0.78Kb) and the other corresponded in size to TRF normal values (7.15±1.2Kb)
  • There was no difference in the TRF length between patients with initial vs. relapse disease
  • Cytogenetic cultures were successfully performed 14 patients
    • of these, 47 % had abnormal karyotypes
    • 58% of patients had the Cyclin D1/IgH rearrangement.
  • Using FISH, all cases showed t(11,14) positive cells (mean: 39%; range: 4-97.2%).
  • Only one TRF peak was observed in 77% of patients with high frequencies of FISH positive cells (≥20%) compared to 33% of those with lower frequencies (<20%) (p<0.01).

Author's Conclusions

These results showed a significant TRF decrease in MCL patients and suggest this parameter as a possible marker reflecting tumor mass.

Clinical/Scientific Implications

Telomere length was shorter in MCL tumor cells than in normal tissue, on average.

The authors found a significant correlation between the number of TRF populations (1 vs. 2) and the percentage of cells that were FISH positive for the Cyclin D1/IgH rearrangement. This may reflect the percentage of tumor cells in the given samples or could be a result of sampling.

The Cyclin D1/IgH rearrangement appears to be an important factor in the pathogenesis of MCL and may represent a potential therapeutic target.

More studies are needed to define if using the TRF assay will be important in following these patients in the future. These studies should define clinical parameters and follow outcome measurements to see if the TRF assay is clinically useful.


News
R-CHOP Benefits Older Mantle-Cell Lymphoma Patients

Aug 9, 2012 - In older patients with mantle-cell lymphoma, a rituximab-based chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by maintenance therapy with rituximab improves survival, according to a study published in the Aug. 9 issue of the New England Journal of Medicine.



I Wish You Knew

How cancer patients have changed my life

View More



Blogs and Web Chats

OncoLink Blogs give our readers a chance to react to and comment on key cancer news topics and provides a forum for OncoLink Experts and readers to share opinions and learn from each other.




OncoLink OncoPilot

Frente a un nuevo diagnóstico de cáncer o de cambiar el curso de su tratamiento actual? Deje que nuestro personal de enfermería cáncer que ayudan a pasar!

Más información