p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV

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,...

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Detalhes bibliográficos
Autores: Valgañon, M. (Mikel)|||/items/a30b1c18-1d53-4680-811c-812d7c7a29aa, Giraldo, P. (P.)|||/items/2917f207-6a0d-4fc9-b024-7470fa8277d4, Aguirre-Ena, X. (Xabier)|||/items/2a000d9c-cb5c-4734-a32c-4fef79998c86, Larrayoz-Ilundáin, M.J. (María José)|||/items/7e29cbb9-798d-4830-bfcf-729a99e05d02, Rubio-Martinez, A. (Araceli)|||/items/994456c3-f421-48bc-ae7d-8139ce6945c5, Rubio-Felix, D. (Daniel)|||/items/154bfc81-d685-4ca5-b76c-05068228ea3a, Calasanz-Abinzano, M.J. (Maria Jose)|||/items/a1f10f5c-06ce-47eb-bfd8-91fb972d8086, Odero, M.D. (Maria Dolores)|||/items/6679bbec-f7dd-480c-a44c-44d7c8493251
Tipo de documento: artigo
Data de publicação:2005
País:España
Recursos:Universidad de Navarra
Repositório:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglês
OAI Identifier:oai:dadun.unav.edu:10171/19493
Acesso em linha:https://hdl.handle.net/10171/19493
Access Level:Acceso aberto
Palavra-chave:Chronic lymphocytic leukaemia
Fludarabine
p53
Methylation
Descrição
Resumo: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.

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