Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP Brazil.
Genet Mol Biol. 2009 Apr;32(2):234-41. doi: 10.1590/S1415-47572009000200005. Epub 2009 Jun 1.
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.
染色体易位是造血肿瘤的特征，可导致不受调控的癌基因表达或基因融合产生新的功能。近年来，在健康个体中已检测到不同的淋巴瘤/白血病相关重排。在本研究中，我们使用反向 PCR 筛查了 100 名健康个体的外周血淋巴细胞中是否存在 MLL（混合谱系白血病）易位。49%的个体显示 MLL 重排。序列分析表明，这些重排是 MLL 易位特异性的，对应 t(4;11)(q21;q23)（66%）和 t(9;11)（20%）。然而，我们的 RT-PCR 未能在人群中检测到任何 t(4;11)(q21;q23)的表达。我们认为，正常个体外周血淋巴细胞中的 11q23 重排可能是由于内源性或外源性 DNA 损伤剂的暴露所致。实际上，MLL 基因对化学诱导损伤的高易感性表明，监测外周血淋巴细胞中与该基因相关的异常可能是评估暴露于遗传毒性应激个体基因组不稳定性的敏感检测方法。
