Mechanisms of relapse in acute leukaemia: involvement of p53 mutated subclones in disease progression in acute lymphoblastic leukaemia

British Journal of Cancer
Y M ZhuH H Russell

Abstract

Mutations of the p53 tumour suppressor gene are infrequent at presentation of both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), being found in between 5-10% of AML and 2-3% of ALL. Here we have studied the frequency of detection of p53 mutations at relapse of both AML and B-precursor ALL. In those patients with detectable mutations at relapse we investigated whether the mutation was detectable at presentation and was thus an early initiating event or whether it had arisen as a late event associated with relapse. Bone marrow samples from 55 adults and children with relapsed AML (n = 41) or ALL (n = 14) were analysed for p53 gene alterations by direct sequencing of exons 5-9. For samples where a p53 mutation was found at relapse, analysis of presentation samples was carried out by direct sequencing of the exon involved, or by allele-specific polymerase chain reaction (PCR) if the mutation could not be detected using direct sequencing. A p53 mutated gene was found at relapse in seven out of 55 cases. The frequency was higher in relapsed ALL (four out of 14 cases; 28.6%) compared to AML (three out of 41 cases; 7.3%). In five out of the seven cases presentation samples were available to study for the p...Continue Reading

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Citations

Oct 24, 2000·Leukemia & Lymphoma·T NaoeH Kiyoi
Jul 7, 2017·Leukemia & Lymphoma·Silvia SalmoiraghiOrietta Spinelli
Jan 15, 2014·Human Mutation·Jitka MalcikovaSarka Pospisilova
Sep 28, 2010·Environmental and Molecular Mutagenesis·Joe ShugaMartyn T Smith
Mar 7, 2002·Journal of Pediatric Hematology/oncology·J GumpS P Hunger
Jan 20, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Joanna SzczepanekMariusz Wysocki
Sep 3, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Mohamed Mohamed Abdel-Aziz
Feb 24, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lee-Yung ShihChung-Chih Tang

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