CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia

Abstract

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.

Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

“…We investigated whether disease stages could be represented by genes that are reported to be highly expressed in myeloid leukemia ( Fig. 1F ) ( Handschuh et al, 2018 ; Landberg et al, 2016 ; Liu et al, 2021 ; Scolnik et al, 2002 ; Xu and Guo, 2020 ). These genes were identified via bulk RNAseq of BM and blood ( STMN1 , KIT , and CDK6 ), The Cancer Genome Atlas Program ( FCGR1A and CDK6 ), or RNAseq of leukemic stem cells ( KIT ).…”

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC

“…Notably, while the majority of transcripts were unaffected by JCS-1 treatment, numerous genes implicated in AML pathogenesis and cell viability were significantly differentially expressed ( p adj < 0.05, |L2FC (log 2 fold change) > 0.6). BCL2, NRAS , and CDK6 , which have all been posited as potential AML therapeutic targets, were downregulated in JCS-1 treated samples relative to DMSO-treated controls. − Given that DcpS has at least one known function independent of its catalytic decapping activity (i.e., control of cytoplasmic miRNA turnover), we next investigated the effect of DcpS degradation versus inhibition on the mRNA pool of MOLM-14 cells (Figure B). Specifically, we were interested to see whether treatment with JCS-1 might also elicit changes in mRNA expression patterns not observed under JCS-2 treatment.…”

One Step Away From Extinction: A Population Genomic Analysis of A Narrow Endemic, Tropical Plant Species

“…Genomic approaches are valuable as they can provide new insights and a better understanding of the amount, distribution, and functional significance of genetic variation in natural populations (Allendorf et al, 2010). As predicted by Funk et al (2012), the use of genomic data is on the rise for species in relation to discussions around conservation (Hawkins et al, 2018;Huy et al, 2018;Lanes et al, 2018;Ball et al, 2020;Bao et al, 2020;Chen et al, 2020;Liu et al, 2020;Zang et al, 2020;Zimmerman et al, 2020;Bradbury et al, 2021). Thus, such data can play a critical role in informing management strategies and policy for species on the verge of extinction, many of which are narrow endemics and prime targets for conservation genomic assessments (Silva et al, 2020).…”