Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Pediatr Blood Cancer. 2011 Mar;56(3):349-52. doi: 10.1002/pbc.22679.
The HLXB9 gene encodes a homeodomain containing transcription factor which has been implicated in the development of both solid and hematological malignancies. In leukemia it is one of the two fused genes, along with ETV6, in a recurrent translocation frequently observed in infant AML.
Here we investigate the role of epigenetic inactivation of the HLXB9 gene in leukemia. Quantitative DNA methylation analysis was performed using the COBRA assay, and qRT-PCR was used to assess the effects of methylation on expression in hematological cell lines and primary ALL samples.
Hypermethylation of the HLXB9 gene was found to be a frequent event in childhood ALL, occurring in 33% of cases. However, it was rarely or never observed in other types of leukemia, including AML, CML, and CLL, with the exception of adult ALL, in which 39% of cases were hypermethylated. Furthermore, hypermethylation of HLXB9 results in loss of expression in hematological cell lines and primary ALL samples.
These results suggest that HLXB9 may have a dual role in childhood leukemia, as an oncogene in infant AML but as a tumor suppressor in childhood ALL.
HLXB9 基因编码含有同源结构域的转录因子，它与实体瘤和血液系统恶性肿瘤的发生有关。在白血病中，它是与 ETV6 一起经常发生于婴儿 AML 的复发性易位的两个融合基因之一。
在这里，我们研究了 HLXB9 基因的表观遗传失活在白血病中的作用。使用 COBRA 检测法进行定量 DNA 甲基化分析，并使用 qRT-PCR 评估甲基化对血液细胞系和原发性 ALL 样本表达的影响。
在儿童 ALL 中发现 HLXB9 基因的高甲基化是一个常见事件，发生在 33%的病例中。然而，在其他类型的白血病中，包括 AML、CML 和 CLL，很少或从未观察到，除了成人 ALL，其中 39%的病例发生高甲基化。此外，HLXB9 的高甲基化导致血液细胞系和原发性 ALL 样本中的表达缺失。
这些结果表明，HLXB9 可能在儿童白血病中具有双重作用，作为婴儿 AML 的癌基因，但作为儿童 ALL 的肿瘤抑制基因。
