Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia
Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia
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DOI：
10.1038/sj.leu.2402354
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发表时间：
2002-02-01
期刊：
影响因子：
11.4
通讯作者：
Roche, J
中科院分区：
文献类型：
--
作者：
Drabkin, H;Parsy, C;Roche, J
我们使用简并RT-PCR筛选和随后的实时定量RT-PCR分析，以检查HOX和TALE家族基因在34例染色体定义的AML中的表达，其结果数据可用。具有良好细胞遗传学特征的AML与总体HOX基因表达低相关，而预后不良的病例则与HOX基因表达高相关。特征性地，包括HOXA 3-HOXA 10的多个HOXA家族成员与HOXB 3、HOXB 6、MEIS 1和PBX 3联合过表达。在FAB亚型AML-M1中也观察到更高水平的表达。Spearmann相关系数表明，许多这些基因的表达水平是高度相关的。虽然我们在这组有限的患者中没有检测到HOX表达与完全缓解率或年龄之间的任何显著相关性，但无事件生存率与HOXA 7之间存在显著相关性，HoxA 9，HoxA 4和HoxA 5有显著性趋势。虽然HOX表达升高的患者表现更差，但也有明显的例外。因此，尽管HOX过表达和临床化疗耐药往往是一致的，但它们并不是密不可分的。我们的研究结果表明，定量HOX分析有可能为AML患者的管理增加新的信息，特别是在缺乏特征性染色体改变的情况下。
We used a degenerate RT-PCR screen and subsequent real-time quantitative RT-PCR assays to examine the expression of HOX and TALE-family genes in 34 cases of chromosomally defined AML for which outcome data were available. AMLs with favorable cytogenetic features were associated with low overall HOX gene expression whereas poor prognostic cases had high levels. Characteristically, multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed in conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression were also observed in the FAB subtype, AML-M1. Spearmann correlation coefficients indicated that the expression levels for many of these genes were highly interrelated. While we did not detect any significant correlations between HOX expression and complete response rates or age in this limited set of patients, there was a significant correlation between event-free survival and HOXA7 with a trend toward significance for HoxA9, HoxA4 and HoxA5. While patients with elevated HOX expression did worse, there were notable exceptions. Thus, although HOX overexpression and clinical resistance to chemotherapy often coincide, they are not inextricably linked. Our results indicate that quantitative HOX analysis has the potential to add new information to the management of patients with AML, especially where characteristic chromosomal alterations are lacking.