Late genetic effects of cancer therapy in cured ALL (acute lymphoblastic leukemia) and non-Hodgkins lymphoma patients as detected by DNA rearrangements

ML Camparoto MSca, MS Brassesco BCa, LPG D'Arce MSca, SS Mello BCa, LG Tone PhDb, GAS Passos PhDc and ET Sakamoto-Hojo PhDa,d.

aDepartamento de Genetica e bDepartamento de Pediatria e Puericultura-HC, Faculdade de Medicina de Ribeirao Preto-USP; cFaculdade de Odontologia de Ribeirao Preto-USP; dDepartamento de Biologia, Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-USP, Universidade de Sao Paulo, Campus de Ribeirao Preto, S.P., BRASIL, E-mail:

AIM: The diagnostic and prognostic significance of chromosomal translocations is already well established. The aims of the present work were to detect numerical and structural alterations (juxtaposition of genes by DNA rearrangements and gene fusions, such as bcr/abl) in lymphocytes from cured pediatric ALL (acute lymphoblastic leukemia) and NHL (non Hodgkin's lymphoma) patients to evaluate the late effects of cancer therapies. METHODS: FISH (fluorescence in situ hybridization) method followed by image system analysis were used for nine patients (2 NHL and 7 ALL) to determine the frequencies of bcr/abl fusion. The hybrid genes (formed by interloci recombination between T cell receptor (TCR-b) joining (J) regions and TCR-g variable (V) regions) were detected by nested PCR with especific primers, followed by dot-blot hybridization analysis and phosphorimaging (23 ALL and 6 NHL patients). A parallel in vitro study was carried out in irradiated-lymphocyte cultures from normal individuals. RESULTS: The frequencies of bcr/abl fusions varied from 0.34 to 3.76/100 cells; extra signals for both genes ranged from zero to 2.25/100 cells; the hybrid TCRb/g genes were detected in 50% of the patients. The irradiated lymphocytes did not show a dose-dependent increase in the frequencies of hybrid genes. CONCLUSIONS: Although no correlation could be found between the period after the therapy conclusion (18-115 months) and the frequencies of DNA rearrangements, the genomic instability observed for some patients is important to detect residual disease and estimate the risk of relapse.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 1.