MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals

• Main Authors: María Sol Brassesco, Ana Paula Montaldi, Diana Ester Gras, Rosane Gomes de Paula Queiroz, Nilce Maria Martinez-Rossi, Luiz Gonzaga Tone, Elza Tiemi Sakamoto-Hojo
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Genética 2009-01-01
• Series: Genetics and Molecular Biology
• Subjects: genomic instability; lymphocytes; MLL rearrangements
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572009000200005

Chromosomal translocations are characteristic of hematopoietic neoplasias and can lead to unregulated oncogene expression or the fusion of genes to yield novel functions. In recent years, different lymphoma/leukemia-associated rearrangements have been detected in healthy individuals. In this study, we used inverse PCR to screen peripheral lymphocytes from 100 healthy individuals for the presence of MLL (Mixed Lineage Leukemia) translocations. Forty-nine percent of the probands showed MLL rearrangements. Sequence analysis showed that these rearrangements were specific for MLL translocations that corresponded to t(4;11)(q21;q23) (66%) and t(9;11) (20%). However, RT-PCR failed to detect any expression of t(4;11)(q21;q23) in our population. We suggest that 11q23 rearrangements in peripheral lymphocytes from normal individuals may result from exposure to endogenous or exogenous DNA-damaging agents. In practical terms, the high susceptibility of the MLL gene to chemically-induced damage suggests that monitoring the aberrations associated with this gene in peripheral lymphocytes may be a sensitive assay for assessing genomic instability in individuals exposed to genotoxic stress.