CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.
CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.
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DOI：
10.3389/fgene.2020.600227
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发表时间：
2020
影响因子：
3.7
通讯作者：
Zeng H
中科院分区：
文献类型：
--
作者：
Liu W;Yi JM;Liu Y;Chen C;Zhang KX;Zhou C;Zhan HE;Zhao L;Morales S;Zhao XL;Zeng H
急性髓系白血病(AML)是一种危害性的血液系统恶性疾病，需要新的成功的治疗方法。细胞周期蛋白依赖性激酶6(CDK6)是一种细胞周期调控酶，在白血病的发生和白血病干细胞(LSC)的维持中起重要作用，有可能预测AML的预后。通过分析公共数据库，我们观察到与健康供者相比，CDK6的信使RNA(MRNA)在AML细胞系和非急性早幼粒细胞白血病(Non-APL)AML患者中显著过表达。此外，在我们验证的队列中，与确诊时相比，获得完全缓解(CR)的AML患者CDK6的表达显著降低。CDK6的表达与外周血母细胞、法美英(FAB)亚型、CCAAT增强子结合蛋白α突变、t(8；21)染色体异常密切相关。然而，CDK6的表达对非APL AML患者预后的临床意义和影响仍不确定。通过Kaplan-Meier分析，我们发现CDK6的表达与非APL AML患者的总生存期(OS)呈负相关。研究还发现，CDK6与CCND2、Dnmt3b、Sox4和IKZF2等促进白血病发生的基因呈正相关，与miR-187、miR-9、miR-582、miR708和miR-362等抗癌microRNAs呈负相关。综上所述，我们的研究显示CDK6可能是非APL AML患者潜在的诊断和预后的生物标志物。
Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), 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 CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 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 CDK6 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 CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2, DNMT3B, SOX4, and IKZF2, 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 CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients.