Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia
2004

Dkk-3 Gene Silencing in Acute Lymphoblastic Leukaemia

Sample size: 183 publication 10 minutes Evidence: high

Author Information

Author(s): Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo J A, Navarro G, Barrios M, Andreu E J, Prosper F, Heiniger A, Torres A

Primary Institution: Reina Sofia Hospital, Cordoba, Spain

Hypothesis

The Dkk-3 gene is silenced by methylation in acute lymphoblastic leukaemia (ALL) and this event is associated with poor prognosis.

Conclusion

The silencing of the Dkk-3 gene by aberrant promoter methylation occurs early in ALL pathogenesis and negatively impacts patient outcomes.

Supporting Evidence

  • Dkk-3 methylation was detected in 33% of patients with ALL.
  • Patients with methylated Dkk-3 had a higher relapse rate compared to those with unmethylated Dkk-3.
  • Restoration of Dkk-3 expression was achieved using a demethylating agent.
  • Dkk-3 methylation was associated with poor disease-free survival rates.
  • Significant concordance was observed between Dkk-3 methylation and Calcitonin methylation.

Takeaway

In some children and adults with a type of blood cancer called ALL, a gene that helps control cell growth is turned off due to a chemical change, which can make the cancer worse.

Methodology

The study involved analyzing DNA and RNA from bone marrow samples of 183 patients diagnosed with ALL, using techniques like methylation-specific PCR and quantitative real-time PCR.

Potential Biases

Potential biases may arise from the selection of patients and the retrospective nature of the study.

Limitations

The study may not account for all genetic and environmental factors influencing ALL outcomes.

Participant Demographics

The study included 183 patients (106 male, 77 female) with a median age of 14.5 years at diagnosis.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1038/sj.bjc.6602008

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication