Analysis of ETV6/RUNX1 fusions for evaluating the late effects of cancer therapy in ALL (acute lymphoblastic leukemia) cured patients.
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.
Brassesco
M S
MS
Departamento de Genética, Faculdade de Medicina de Ribeirão Preto-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Camparoto
M L
ML
Tone
L G
LG
Sakamoto-Hojo
E T
ET
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured / Q000648:ultrastructure; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics* / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000648:ultrastructure; D003131:Combined Modality Therapy; D050676:Core Binding Factor Alpha 2 Subunit; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D018365:Neoplasm, Residual; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics; D009360:Neoplastic Cells, Circulating; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000097:blood / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D012074:Remission Induction; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein