PMID- 15162063 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20151119 IS - 1424-859X (Electronic) IS - 1424-8581 (Linking) VI - 104 IP - 1-4 DP - 2004 TI - Analysis of ETV6/RUNX1 fusions for evaluating the late effects of cancer therapy in ALL (acute lymphoblastic leukemia) cured patients. PG - 346-51 AB - Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in childhood. The improvements of therapies have increased the number of long-term survivors. However, an increased incidence of secondary neoplasias has been observed in this cohort. Our purpose was to evaluate the late effects of cancer therapy in cured patients previously treated for ALL, considering previous reports on the occurrence of gene fusions as putative markers of chromosomal instability. Twelve ALL patients (aged 5 to 16 years) and twelve healthy subjects (aged 18 to 22 years) were studied for the presence of ETV6/RUNX1 (TEL/AML1) translocations, which were detected by FISH (fluorescence in situ hybridization). The blood samples were collected months or years after completion of the therapy, and the frequencies of gene fusions in lymphocytes were compared with those obtained retrospectively for bone marrow samples at the time of diagnosis, and also for the control group. It was demonstrated that ETV6/RUNX1 gene fusion was a frequent event (0.59-1.84/100 cells) in peripheral blood lymphocytes from normal individuals and the ALL patients who underwent chemotherapy showed significantly (P = 0.0043) increased frequencies (0.62-3.96/100 cells) of the rearrangement when compared with the control groups (patients at diagnosis and healthy subjects). However, a significant difference was not found between the groups of patients at diagnosis and healthy subjects, when the two patients who were positive for the rearrangement were excluded. Therefore, increased frequencies of ETV6/RUNX1 fusions in ALL cured patients indicate the influence of previous exposure to anti-cancer drugs, and they may represent an important genetic marker for estimating the risk of relapse, or development of secondary neoplasias. CI - Copyright 2003 S. Karger AG, Basel FAU - Brassesco, M S AU - Brassesco MS AD - Departamento de Genetica, Faculdade de Medicina de Ribeirao Preto-USP, Universidade de Sao Paulo, Ribeirao Preto, SP, Brasil. FAU - Camparoto, M L AU - Camparoto ML FAU - Tone, L G AU - Tone LG FAU - Sakamoto-Hojo, E T AU - Sakamoto-Hojo ET LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Cytogenet Genome Res JT - Cytogenetic and genome research JID - 101142708 RN - 0 (Biomarkers, Tumor) RN - 0 (Core Binding Factor Alpha 2 Subunit) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (TEL-AML1 fusion protein) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Biomarkers, Tumor/*analysis/blood/genetics MH - Bone Marrow/pathology MH - Cells, Cultured/ultrastructure MH - Child, Preschool MH - Chromosomes, Human, Pair 12/*genetics/ultrastructure MH - Chromosomes, Human, Pair 21/*genetics/ultrastructure MH - Combined Modality Therapy MH - Core Binding Factor Alpha 2 Subunit MH - Cranial Irradiation MH - Female MH - Humans MH - Lymphocytes/ultrastructure MH - Male MH - Neoplasm, Residual MH - Neoplasms, Second Primary/chemically induced/genetics MH - *Neoplastic Cells, Circulating MH - Oncogene Proteins, Fusion/*analysis/blood/genetics MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/blood/drug therapy/*genetics/pathology/radiotherapy MH - Remission Induction MH - *Translocation, Genetic EDAT- 2004/05/27 05:00 MHDA- 2004/11/02 09:00 CRDT- 2004/05/27 05:00 PHST- 2003/08/20 00:00 [received] PHST- 2003/11/28 00:00 [accepted] PHST- 2004/05/27 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/05/27 05:00 [entrez] AID - 77514 [pii] AID - 10.1159/000077514 [doi] PST - ppublish SO - Cytogenet Genome Res. 2004;104(1-4):346-51. doi: 10.1159/000077514.