Yang Hui, Maddipoti Sirisha, Quesada Andres, Bohannan Zachary, Cabrero Calvo Monica, Colla Simona, Wei Yue, Estecio Marcos, Wierda William, Bueso-Ramos Carlos, Garcia-Manero Guillermo
a Department of Leukemia , University of Texas MD Anderson Cancer Center , Houston , TX , USA.
b Department of Molecular Carcinogenesis , University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Leuk Lymphoma. 2015;56(12):3426-33. doi: 10.3109/10428194.2015.1034705. Epub 2015 May 26.
Histone deacetylase (HDAC) inhibitors are well-characterized anti-leukemia agents and HDAC gene expression deregulation has been reported in various types of cancers. This study sought to characterize HDAC gene expression patterns in several types of leukemia. To do so, a systematic study was performed of the mRNA expression of all drug-targetable HDACs for which reagents were available. This was done by real-time PCR in 24 leukemia cell lines and 39 leukemia patients, which included AML, MDS and CLL patients, some of whom received HDAC inhibitor treatment. Among the samples analyzed, there was no discernible pattern in HDAC expression. HDAC expression was generally increased in CLL patients, except for HDAC2 and HDAC4. HDAC expression was also generally increased in VPA-treated MOLT4 cells. However, this increased expression was not seen in AML patients treated with vorinostat. In summary, increased HDAC expression was noted in CLL patients in general, but the HDAC expression patterns in myeloid malignancies appear to be heterogeneous, which implies that the role of HDACs in leukemia may be related to global expression or protein function rather than specific expression patterns.
组蛋白去乙酰化酶(HDAC)抑制剂是特征明确的抗白血病药物,并且在各种类型的癌症中都报道了HDAC基因表达失调。本研究旨在描述几种类型白血病中的HDAC基因表达模式。为此,对所有有试剂可用的可药物靶向HDAC的mRNA表达进行了系统研究。这是通过对24种白血病细胞系和39例白血病患者(包括急性髓系白血病(AML)、骨髓增生异常综合征(MDS)和慢性淋巴细胞白血病(CLL)患者,其中一些接受了HDAC抑制剂治疗)进行实时PCR来完成的。在分析的样本中,HDAC表达没有明显的模式。除HDAC2和HDAC4外,CLL患者的HDAC表达通常增加。在丙戊酸(VPA)处理的MOLT4细胞中,HDAC表达也通常增加。然而,在用伏立诺他治疗的AML患者中未观察到这种表达增加。总之,一般在CLL患者中观察到HDAC表达增加,但髓系恶性肿瘤中的HDAC表达模式似乎是异质性的,这意味着HDAC在白血病中的作用可能与整体表达或蛋白质功能有关,而不是与特定的表达模式有关。