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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Genética > DA - CIMA - Oncología - Genética - Artículos de revista >

p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV
Authors: Valgañon, M. (Mikel)
Giraldo, P. (P.)
Aguirre, X. (Xavier)
Larrayoz, M.J. (María J.)
Rubio-Martinez, A. (Araceli)
Rubio-Felix, D. (Daniel)
Calasanz, M.J. (María José)
Odero, M.D. (María D.)
Keywords: Chronic lymphocytic leukaemia
Fludarabine
p53
Methylation
Issue Date: 2005
Publisher: Blackwell Publishing
Publisher version: http://bit.ly/v09WrK
ISSN: 1365-2141
Citation: Valgañon M, Giraldo P, Agirre X, Larrayoz MJ, Rubio-Martinez A, Rubio-Felix D, et al. p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV. Br J Haematol 2005 Apr;129(1):53-59
Abstract
Abnormalities of p53 have been associated with short survival and non-response to therapy in chronic lymphocytic leukaemia (CLL). We have evaluated the rate of response to fludarabine as first-line therapy in 54 patients with advanced stage CLL, analysing the cytogenetic profile, aberrations in p53, including the methylation status of its promoter, and the immunoglobulin heavy-chain variable-region (IGVH) mutation status. According to the advanced stage of the disease in this series, 75% of patients presented genetic aberrations associated with poor prognosis: del(17p) and/or del(11q), and no-mutated IGVH genes. Ten patients (18.5%) had methylation in the promoter region of p53. Eighty-three per cent of patients treated achieved a response, with a high rate of complete remission (47.6%). Although we found a significant correlation between failures and the presence of p53 aberrations (P = 0.0065), either with methylation (P = 0.018) or deletion (P = 0.015), 64% of the patients with aberrations in this gene responded to treatment (11/17), suggesting that fludarabine induces high remission rates, even in these patients. This is the first time that the significance of p53 promoter methylation status is described in this pathology, and our data support that this epigenetic phenomenon could be involved in the pathogenesis and clinical evolution of CLL.
Permanent link: http://hdl.handle.net/10171/19493
Appears in Collections:DA - CIMA - Oncología - Genética - Artículos de revista
DA - Ciencias - Genética - Artículos de revista

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