Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Cell cycle alterations in Mantle cell lymphoma

The different partners of the project (Universities of Barcelona, Munich, and Würzburg) have developed a comprehensive analysis of cell cycle regulators in the pathogenesis of MCL and its potential values in the management of the patients. Thus, we have demonstrated that deletions of INK4/ARF locus and p53 mutations are the most common alterations in highly proliferative MCL. p15INK4b is highly hypermethylated but p16INK4a methylation is rare. BMI-1, an upstream regulator of INK4a/ARF locus, is amplified and over expressed in MCL with no alterations in this locus.

Amplification and over expression of CDK4 seems to be an alternative mechanism to INK4a/ARF locus inactivation but occurs in cases with p53 mutations. Tetraploidization is a frequent phenomenon in MCL but rare in other lymphomas. Anomalies in the number and conformation of centromeres have been demonstrated in MCL associated with tetraploid clones. Inactivation of ATM and CHK2 genes seem to be associated with increasing number of chromosomal imbalances in these tumors.

These results indicate that genetic alterations in all these elements are probably the workforce driving the aggressive behaviour of these tumors, provide a new framework to establish more accurate prognostic parameters, and define new potential therapeutic targets to improve the outcome of the patients.

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Hospital Clinic, University of Barcelona
Villaroel 170
08036 Barcelona
Spain
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