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

Author(s)

Brassesco, Maria Sol ^{[1, 2]} ; Montaldi, Ana Paula ^[2] ; Gras, Diana Ester ^[2] ; de Paula Queiroz, Rosane Gomes ^[1] ; Martinez-Rossi, Nilce Maria ^[2] ; Tone, Luiz Gonzaga ^[1] ; Sakamoto-Hojo, Elza Tiemi ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Dept Puericultura & Pediat, Fac Med Ribeirao Preto, BR-14040900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14040900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Biol, Fac Filosofia Ciencias & Letras, BR-14040900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 32, n. 2, p. 234-241, 2009.
• Web of Science Citations: 6

Abstract

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. (AU)