Salvati P D, Ranford P R, Ford J, Kees U R
Division of Children's Leukaemia and Cancer Research, TVW Telethon Institute for Child Health Research, West Perth, Australia.
Oncogene. 1995 Oct 5;11(7):1333-8.
Based on cytogenetic analysis, chromosomal translocations involving band 10q24 occur in 4-7% of T-cell acute lymphoblastic leukemia (T-ALL). The HOX11 gene is located in this chromosomal band and is activated by translocations t(10;14) (q24;q11) and t(7;10) (q35;q24). Ectopic expression of the HOX11 gene appears to be involved in the development of T-cell tumors. The aim of this study was to determine the frequency of HOX11 activation in pediatric ALL patients and to correlate gene expression with ALL immunophenotype. None of 53 B-lineage ALLs was positive for HOX11 expression, however, Northern blot and RT-PCR analysis revealed that four of 12 T-ALLs (33%) showed expression of the gene. In order to assess whether HOX11 expression is present in other pediatric malignancies we examined a panel of 20 tumor cell lines established from solid tumors and leukemias, but none of them showed expression of HOX11. Using our RT-PCR method we confirmed that HOX11 expression is not detectable in normal T-cells. These findings indicate that HOX11 expression in pediatric ALL is exclusive to T-ALL and does not occur in B-lineage ALL. The frequency detected by molecular techniques was significantly higher than the frequency reported in the literature based on cytogenetic analysis. These results support the notion that ectopic expression of the HOX11 homeobox gene is a crucial step in T-cell tumorigenesis.
基于细胞遗传学分析，涉及10q24带的染色体易位发生在4%至7%的T细胞急性淋巴细胞白血病（T-ALL）中。HOX11基因位于该染色体带，可通过t(10;14)(q24;q11)和t(7;10)(q35;q24)易位被激活。HOX11基因的异位表达似乎参与了T细胞肿瘤的发生发展。本研究的目的是确定小儿ALL患者中HOX11激活的频率，并将基因表达与ALL免疫表型相关联。53例B系ALL中无HOX11表达阳性者，然而，Northern印迹和RT-PCR分析显示，12例T-ALL中有4例（33%）显示该基因表达。为了评估HOX11表达是否存在于其他小儿恶性肿瘤中，我们检测了一组由实体瘤和白血病建立的20种肿瘤细胞系，但它们均未显示HOX11表达。使用我们的RT-PCR方法，我们证实正常T细胞中检测不到HOX11表达。这些发现表明，小儿ALL中的HOX11表达仅见于T-ALL，而不见于B系ALL。分子技术检测到的频率显著高于基于细胞遗传学分析的文献报道频率。这些结果支持了HOX11同源盒基因的异位表达是T细胞肿瘤发生关键步骤的观点。
