Institute of Human Genetics, Polish Academy of Sciences, PL–60-479 Poznan, Poland.
Acta Haematol. 2013;129(4):232-7. doi: 10.1159/000345407. Epub 2013 Jan 11.
The etiopathogenesis of childhood leukemia is not fully understood. It is suggested that endogenous viral sequences may play a role in leukemogenesis. Human endogenous retroviruses (HERVs) constitute about 8% of the human genome. Most HERVs are dysfunctional because of numerous mutations and deletions. Some HERVs, however, contain sequences capable of transcription. In patients with leukemia, the presence of antibodies against HERV-K has been identified, which could suggest increased expression of HERV-K in leukemic cells. To elucidate the role of endogenous retroviruses in leukemogenesis, studies were undertaken to assess env gene expression of HERV-K and HERV-W in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
This study was performed in 170 children with ALL, 38 subjects with AML, and 30 healthy subjects. Expression of the env gene of HERV-K and HERV-W and the control gene ACTB was studied by real-time PCR using specific oligonucleotide primers and SYBR Green marker. Env gene expression was assessed on the basis of the absolute threshold-Ct, as well as normalized against ACTB expression and double normalized expression relative to ACTB and reference cells - normal peripheral blood lymphocytes (PBL). Env gene expression of HERV-K normalized against ACTB, as well as double normalized expression relative to ACTB and normal PBL, was significantly higher only in AML. There were no statistically significant differences in env gene expression of HERV-W normalized to ACTB in ALL and AML as compared to normal PBL.
High normalized expression of the env gene of HERV-K in AML strongly suggests a possible contribution of this gene in the pathogenesis of AML.
儿童白血病的发病机制尚不完全清楚。内源性病毒序列可能在白血病的发生中起作用。人类内源性逆转录病毒(HERV)约占人类基因组的 8%。由于大量的突变和缺失,大多数 HERV 是无功能的。然而,一些 HERV 包含能够转录的序列。在白血病患者中,已经发现针对 HERV-K 的抗体存在,这可能表明白血病细胞中 HERV-K 的表达增加。为了阐明内源性逆转录病毒在白血病发生中的作用,我们进行了研究,以评估儿童急性淋巴细胞白血病(ALL)和急性髓系白血病(AML)中 HERV-K 和 HERV-W 的 env 基因表达。
本研究纳入了 170 例 ALL 患儿、38 例 AML 患儿和 30 例健康对照。采用实时 PCR 技术,使用特异性寡核苷酸引物和 SYBR Green 标记物,研究 HERV-K 和 HERV-W 的 env 基因以及对照基因 ACTB 的表达。根据绝对阈值-Ct 评估 env 基因的表达,并与 ACTB 表达进行归一化,以及与 ACTB 和参考细胞-正常外周血淋巴细胞(PBL)进行双重归一化。仅在 AML 中,HERV-K 的 env 基因相对于 ACTB 的归一化表达以及相对于 ACTB 和正常 PBL 的双重归一化表达显著升高。与正常 PBL 相比,ALL 和 AML 中 HERV-W 的 env 基因相对于 ACTB 的表达无统计学差异。
AML 中 HERV-K 的 env 基因高表达强烈提示该基因可能在 AML 的发病机制中起作用。