Cytogenetic and molecular analysis of MLL rearrangements in acute lymphoblastic leukaemia survivors

Autor(es)

Brassesco, Maria S. ^{[1, 2]} ; Montaldi, Ana P. ^[1] ; Gras, Diana E. ^[1] ; Camparoto, Marjori L. ^[1] ; Martinez-Rossi, Nilce M. ^[1] ; Scrideli, Carlos A. ; Tone, Luiz G. ; Sakamoto-Hojo, Elza T. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto USP, Dept Genet, BR-14040901 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto USP, Dept Pediat & Puericultura, BR-14040901 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret USP, Dept Biol, BR-14040901 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MUTAGENESIS; v. 24, n. 2, p. 153-160, MAR 2009.
• Citações Web of Science: 9

Resumo

The successful treatment of paediatric malignancies by multimodal therapy has improved outcomes for children with cancer, especially those with acute lymphoblastic leukaemia (ALL). Second malignant neoplasms, however, represent a serious complication after treatment. Depending on dosage, 2-12% of patients treated with topoisomerase II inhibitors and/or alkylating agents develop treatment-related acute myeloid leukaemia characterized by translocations at 11q23. Our goal was to study MLL rearrangements in peripheral lymphocytes using cytogenetic and molecular methods in order to evaluate the late effects of cancer therapy in patients previously treated for childhood ALL. Chromosomal rearrangements at 11q23 were analysed in cytogenetic preparations from 49 long-term ALL survivors and 49 control individuals. Patients were subdivided depending on the inclusion or omission of topoisomerase II inhibitors (VP-16 and/or VM-26) in their treatment protocol. The statistical analysis showed significant (P = 0.007) differences between the frequency of translocations observed for the groups of patients and controls. These differences were also significant (P = 0.006) when the groups of patients (independent of the inclusion of topoisomerase II inhibitors) and controls were compared (P = 0.006). The frequencies of extra signals, however, did not differ between groups of patients and controls. Several MLL translocations were detected and identified by inverse polymerase chain reaction, followed by cloning and sequencing. Thirty-five patients (81%) presented putative translocations; among those, 91% corresponded with t(4;11) (q21;q23), while the other 9% corresponded with t(11;X), t(8;11)(q23;q23) and t(11;16). Our results indicate an increase in MLL aberrations in childhood ALL survivors years after completion of therapy. The higher frequency in this cohort might be associated with therapy using anti-tumoural drugs, independent of the inclusion of topoisomerase II inhibitors. Even though the biological significance of these rearrangements needs further investigation, they demonstrate a degree of genome instability, indicating the relevance of cytogenetic and molecular studies during the follow-up of patients in complete clinical remission. (AU)

• Processo FAPESP: 02/13317-8 - Estudo citogenetico e molecular da instabilidade genomica em resposta a lesoes induzidas no dna pela radiacao ionizante e compostos antitumorais em celulas humanas.
• Beneficiário: Elza Tiemi Sakamoto Hojo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 03/01915-0 - Análise citogenética e molecular de translocações cromossômicas no gene MLL para avaliar os efeitos tardios da quimioterapia em linfócitos de pacientes em alta que apresentaram Leucemia Linfoide Aguda na infância
• Beneficiário: María Sol Brassesco Annichini
• Modalidade de apoio: Bolsas no Brasil - Doutorado