HOXB1 恢复表达促进 HL60 白血病细胞系的凋亡和分化。

HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line.

机构信息

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.

出版信息

Cancer Cell Int. 2013 Oct 22;13(1):101. doi: 10.1186/1475-2867-13-101.

BACKGROUND

Homeobox (HOX) genes deregulation has been largely implicated in the development of human leukemia. Among the HOXB cluster, HOXB1 was silent in a number of analyzed acute myeloid leukemia (AML) primary cells and cell lines, whereas it was expressed in normal terminally differentiated peripheral blood cells.

METHODS

We evaluated the biological effects and the transcriptome changes determined by the retroviral transduction of HOXB1 in the human promyelocytic cell line HL60.

RESULTS

Our results suggest that the enforced expression of HOXB1 reduces cell growth proliferation, inducing apoptosis and cell differentiation along the monocytic and granulocytic lineages. Accordingly, gene expression analysis showed the HOXB1-dependent down-regulation of some tumor promoting genes, paralleled by the up-regulation of apoptosis- and differentiation-related genes, thus supporting a tumor suppressor role for HOXB1 in AML. Finally, we indicated HOXB1 promoter hypermethylation as a mechanism responsible for HOXB1 silencing.

CONCLUSIONS

We propose HOXB1 as an additional member of the HOX family with tumour suppressor properties suggesting a HOXB1/ATRA combination as a possible future therapeutic strategy in AML.

背景

同源盒（HOX）基因失调在人类白血病的发展中起着重要作用。在 HOXB 簇中，HOXB1 在许多分析的急性髓系白血病（AML）原代细胞和细胞系中沉默，而在正常终末分化的外周血细胞中表达。

方法

我们评估了逆转录病毒转导 HOXB1 在人早幼粒细胞白血病细胞系 HL60 中引起的生物学效应和转录组变化。

结果

我们的结果表明，强制表达 HOXB1 可降低细胞生长增殖，诱导细胞凋亡，并沿着单核细胞和粒细胞谱系分化。相应地，基因表达分析表明，HOXB1 依赖性下调一些促进肿瘤的基因，同时上调凋亡和分化相关基因，因此支持 HOXB1 在 AML 中作为肿瘤抑制因子的作用。最后，我们指出 HOXB1 启动子超甲基化是 HOXB1 沉默的机制。