AUTHOR=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 

TITLE=CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.600227

DOI=10.3389/fgene.2020.600227

ISSN=1664-8021

ABSTRACT=<p>Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (<italic>CDK6</italic>), 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 <italic>CDK6</italic> were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, <italic>CDK6</italic> 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 <italic>CDK6</italic> 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 <italic>CDK6</italic> expression on the prognosis of non-APL AML patients remain uncertain. We found that <italic>CDK6</italic> expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. <italic>CDK6</italic> was also found to be positively associated with genes identified to contribute to the development of leukemia, including <italic>CCND2</italic>, <italic>DNMT3B</italic>, <italic>SOX4</italic>, and <italic>IKZF2</italic>, 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 <italic>CDK6</italic> might be a potential diagnostic and prognostic biomarker in non-APL AML patients.</p>