PURPOSE: To quantitate methylation of the CpG island of the promoter region of the p15 gene in childhood acute lymphoblastic leukemia (ALL) and explore its effect on prognosis. METHODS: We assessed methylation of the CpG island on the p15 gene in bone marrow mononuclear cells in 93 ALL cases and in a control group of 20 children with idiopathic thrombocytopenia (ITP) by restriction enzyme Eco52I digestion combined with polymerase chain reaction techniques. We explored the effect of varying levels of methylation on event-free survival (EFS). RESULTS: The mean methylation level was 25 % in de novo ALL and significantly higher than the control group 2 %, P < 0.01). Forty-two percent of cases (39/93) had hypermethylation (level over 10 %). Fifty-seven percent (12/21) and 38 % (27/72) T- and precursor-B ALL patients had hypermethylation (not significant). For all patients, the 8-year EFS was (83 ± 4) %, standard risk (91 ± 4) %, intermediate risk (IR) (82 ± 5) %, and high risk (HR) (43 ± 19) % (χ(2) = 11.58, P < 0.01). Hypermethylation was associated with a lower 8-year EFS (71 ± 7 vs. 91 ± 4 %, P = 0.02) in univariate analyses. CONCLUSIONS: Children with ALL have higher levels of p15 CpG island methylation than a control group of children with ITP. Among children with ALL, hypermethylation was associated with inferior EFS. Higher levels of p15 CpG island methylation may be a poor prognostic marker in childhood ALL.
PURPOSE: To quantitate methylation of the CpG island of the promoter region of the p15 gene in childhood acute lymphoblastic leukemia (ALL) and explore its effect on prognosis. METHODS: We assessed methylation of the CpG island on the p15 gene in bone marrow mononuclear cells in 93 ALL cases and in a control group of 20 children with idiopathic thrombocytopenia (ITP) by restriction enzyme Eco52I digestion combined with polymerase chain reaction techniques. We explored the effect of varying levels of methylation on event-free survival (EFS). RESULTS: The mean methylation level was 25 % in de novo ALL and significantly higher than the control group 2 %, P < 0.01). Forty-two percent of cases (39/93) had hypermethylation (level over 10 %). Fifty-seven percent (12/21) and 38 % (27/72) T- and precursor-B ALL patients had hypermethylation (not significant). For all patients, the 8-year EFS was (83 ± 4) %, standard risk (91 ± 4) %, intermediate risk (IR) (82 ± 5) %, and high risk (HR) (43 ± 19) % (χ(2) = 11.58, P < 0.01). Hypermethylation was associated with a lower 8-year EFS (71 ± 7 vs. 91 ± 4 %, P = 0.02) in univariate analyses. CONCLUSIONS:Children with ALL have higher levels of p15 CpG island methylation than a control group of children with ITP. Among children with ALL, hypermethylation was associated with inferior EFS. Higher levels of p15 CpG island methylation may be a poor prognostic marker in childhood ALL.
Authors: Jose Roman-Gomez; Antonio Jimenez-Velasco; Xabier Agirre; Juan A Castillejo; German Navarro; Maria J Calasanz; Leire Garate; Edurne San Jose-Eneriz; Lucia Cordeu; Felipe Prosper; Anabel Heiniger; Antonio Torres Journal: Clin Cancer Res Date: 2006-08-15 Impact factor: 12.531
Authors: Jose Roman-Gomez; Antonio Jimenez-Velasco; Juan A Castillejo; Xabier Agirre; Manuel Barrios; German Navarro; Francisco J Molina; Maria J Calasanz; Felipe Prosper; Anabel Heiniger; Antonio Torres Journal: Blood Date: 2004-06-15 Impact factor: 22.113
Authors: Shuchi Agrawal; Matthias Unterberg; Steffen Koschmieder; Udo zur Stadt; Uta Brunnberg; Walter Verbeek; Thomas Büchner; Wolfgang E Berdel; Hubert Serve; Carsten Müller-Tidow Journal: Cancer Res Date: 2007-02-01 Impact factor: 12.701