Liu Wei, Yi Jin-Mou, Liu Yi, Chen Cong, Zhang Kai-Xuan, Zhou Cheng, Zhan Hui-En, Zhao Liang, Morales Stephanie, Zhao Xie-Lan, Zeng Hui
Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.
Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Front Genet. 2021 Feb 1;11:600227. doi: 10.3389/fgene.2020.600227. eCollection 2020.
Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of was tightly correlated with peripheral blood blasts, French-American-British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of expression on the prognosis of non-APL AML patients remain uncertain. We found that expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan-Meier analysis. was also found to be positively associated with genes identified to contribute to the development of leukemia, including , , , and , as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that might be a potential diagnostic and prognostic biomarker in non-APL AML patients.
急性髓系白血病(AML)是一种具有威胁性的血液系统恶性疾病,需要新的成功治疗方法。细胞周期蛋白依赖性激酶6()是一种细胞周期调节酶,在白血病发生和白血病干细胞(LSC)维持中起重要作用,具有预测AML预后的潜力。通过分析公共数据库,我们观察到与健康供体相比,在AML细胞系和非急性早幼粒细胞白血病(非APL)AML患者中,的信使核糖核酸(mRNA)水平显著过表达。此外,在我们验证的队列中,与诊断时相比,达到完全缓解(CR)的AML患者中表达显著降低。的表达与外周血原始细胞、法国-美国-英国(FAB)亚型、CCAAT增强子结合蛋白α(CEBPA)突变以及t(8;21)染色体异常密切相关。然而,表达对非APL AML患者预后的临床意义和影响仍不确定。我们使用Kaplan-Meier分析发现,在非APL AML患者中,表达与总生存期(OS)呈负相关。还发现与已确定有助于白血病发生的基因呈正相关,包括、、、和,以及与抗癌微小RNA呈负相关,包括miR-187、miR-9、miR-582、miR708和miR-362。总之,我们的研究表明,可能是非APL AML患者潜在的诊断和预后生物标志物。