ZAP-70 intron1 DNA methylation status: Determination by pyrosequencing in B chronic lymphocytic leukemia

Sylvain Chantepie (1) , Dominique Vaur (2) , Christoph Grunau (3) , Véronique Salaün (4) , Mélanie Briand (5) , Jean-Jacques Parienti (6) , Natacha Heutte (7) , Stéphane Cheze (8) , Mikel Roussel (9) , Pascal Gauduchon (5) , Michel M. Leporrier (10) , Sophie E. Krieger (11)

1 IHBN - Institut d'Hématologie de Basse-Normandie
2 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
3 IHPE - Interactions Hôtes-Pathogènes-Environnements
4 AOROC - Archéologie et Philologie d'Orient et d'Occident
5 GRECAN - Groupe Régional d'Etudes sur le CANcer
6 UBRC - Unité de Biostatistique et de Recherche Clinique
7 CETAPS - Centre d’études des transformations des activités physiques et sportives
8 CHU Caen
9 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
10 LDM-TEP - Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons
11 Interaction virus-hôte et maladies du foie

ZAP-70 expression is a strong prognostic indicator in chronic lymphocytic leukemia. However, ZAP-70 quantification by flow cytometry lacks sufficient standardization. Based upon the correlation between ZAP-70 expression and its gene methylation status, we have developed a quantitative pyrosequencing assay for the determination of ZAP-70 methylation adapted for routine use. Methylation in four CpG pairs (C-223, C-243, C-254, and C-267) in the first intron of ZAP-70 is associated with repression of ZAP-70. Moreover, it correlates with CD38 expression (n = 111, p < .0001), IgHv mutation status (n = 106, p < .0001), time to treatment (p < .0001), and overall survival (p = .0014). Pyrosequencing of ZAP-70 provides a good alternative to flow cytometry.

Domaines: Sciences du Vivant [q-bio]; Cancer

Sylvain Chantepie, Dominique Vaur, Christoph Grunau, Véronique Salaün, Mélanie Briand, et al.. ZAP-70 intron1 DNA methylation status: Determination by pyrosequencing in B chronic lymphocytic leukemia. Leukemia Research, 2010, 34 (6), pp.800-808. ⟨10.1016/j.leukres.2009.10.018⟩. ⟨hal-02358614⟩