Mata J F, Scrideli C A, Queiroz R P, Mori B O, Emerenciano M, Pombo-de-Oliveira M S, Tone L G
Departamento de Pediatria e Puericultura, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2006 Nov;39(11):1417-23. doi: 10.1590/s0100-879x2006001100005.
Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of <or=0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.
婴儿急性淋巴细胞白血病（IALL）的特征为混合谱系白血病（MLL）基因重排、独特的基因表达谱、预后不良和耐药性。一个例外是阿糖胞苷（Ara-C），IALL细胞似乎对其更敏感。我们对64名巴西ALL儿童白血病原始淋巴细胞中Ara-C关键酶的mRNA表达进行了定量，其中15名儿童存在MLL基因重排，并将其与临床和生物学特征相关联。诊断基于形态学标准和使用单克隆抗体的免疫表型分析。通过常规细胞遗传学分析、RT-PCR和/或荧光原位杂交检测MLL基因重排。使用SYBR Green I通过实时定量PCR测定DCK和HENT1的表达水平。通过标准曲线法进行相对定量。结果通过Mann-Whitney检验和Fisher精确检验进行分析。P值≤0.05被认为具有统计学意义。与MLL种系ALL儿童相比，MLL基因重排ALL儿童的DCK和HENT1表达水平显著降低（分别为P = 0.0003和0.03）。我们的结果与之前关于HENT1 mRNA表达的结果不同，之前的研究观察到MLL基因重排白血病中HENT1表达水平较高。总之，在所研究的样本中，MLL阳性儿童中与Ara-C代谢相关的基因表达较低，这表明这些基因的表达谱存在人群差异，尤其是HENT1。
