Myeloid Cell Leukemia-1 Gene Expression and Clinicopathological Features in Myelodysplastic Syndrome

F. Zaker, M. J. Sharifi, N. Nasiri, M. Yaghmaie, Soodeh Namjoo
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Abstract

Background and Aims: Myeloid cell leukemia-1 (Mcl-1) plays a pivotal role in the survival of hematologic and solid tumors, and is known as a substantial oncogene. Studies have demonstrated the altered expression of Mcl-1 has been linked to malignancy development and poor prognosis. In this research, we have studied the expression of Mcl-1 mRNA in myelodysplastic syndrome (MDS) patients and determined association with clinico-pathological factors, MDS subgroups as well as international prognostic scoring system. Materials and Methods: The relative level of Mcl-1 was determined by real time quantitative real-time polymerase chain reaction and gene expression normalized to Glyceraldehyde-3-phosphate dehydrogenase. Results: Results indicated amplification of mRNA encoding Mcl-1 in 100% of the cases. The higher level of Mcl-1 existed in MDS patients compared with the healthy controls but there was no statistically difference of Mcl-1 expression between these groups. Fold change in gene expression was higher in advanced stage MDS, high risk MDS, cases with >5% blast and LDH >400 to their corresponding groups. In addition, the correlation between gene expression and cytogenetic prognostic subgroups was statistically significant (p=0.043). Conclusions: In the present study, we showed that Mcl-1 is expressed in MDS independent of the World Health Organization subgroup and international prognostic scoring system. Therefore, Mcl-1 may be up-regulated already in early stages of leukemogenesis.
髓样细胞白血病-1基因在骨髓增生异常综合征中的表达及临床病理特征
背景与目的:髓系细胞白血病-1 (Myeloid cell leukemia-1, Mcl-1)在血液学和实体肿瘤的生存中起着关键作用,是一种重要的致癌基因。研究表明,Mcl-1表达的改变与恶性肿瘤的发展和预后不良有关。在本研究中,我们研究了Mcl-1 mRNA在骨髓增生异常综合征(MDS)患者中的表达,并确定了其与临床病理因素、MDS亚群以及国际预后评分系统的关系。材料与方法:采用实时定量实时聚合酶链反应测定Mcl-1的相对水平,并将基因表达归一化为甘油醛-3-磷酸脱氢酶。结果:100%的病例均有Mcl-1编码mRNA扩增。MDS患者的Mcl-1表达水平高于健康对照组,但两组间Mcl-1表达水平无统计学差异。晚期MDS、高危MDS、>5% blast和LDH >400组的基因表达倍数变化较高。此外,基因表达与细胞遗传学预后亚组之间的相关性有统计学意义(p=0.043)。结论:在本研究中,我们发现Mcl-1在MDS中表达独立于世界卫生组织亚组和国际预后评分系统。因此,Mcl-1可能已经在白血病发生的早期阶段上调。
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