CMK-86

microRNA-155-5p Alters TNF Signaling, Affecting CMK-86 Cell Viability

Down syndrome (DS) significantly elevates the risk of acute leukemia, especially AML-DS, due to trisomy 21's impact on hematopoiesis. Understanding the transition from transient leukemia to AML-DS is crucial. Sas et al. applied functional enrichment analysis to assess interactions among chromosome 21 genes, miR-155, and signaling pathways. They performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome. And the results showed that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling. Then, to investigate if microRNA-155 mimic and inhibitor significantly affects CMK-86 cell line viability they performed MTS assay. Cell viability was measured after transfection with microRNA-155-5p using MTS assay at 24, 48, 72- and 96-hours post transfection. According to the obtained results, we observed that the modifications occur at 24 and 48h were slightly modified, meanwhile after 72- and 96-hours statistically significant inhibition of cell viability were observed (Fig.1).

Fig. 1. Cell proliferation assessment following transfection with the mimic and inhibitor of miR-155-5p (Sas V, Pasca S, et al., 2020).

Efficacy of CDK4/6 inhibitors in t(8;21) AML cell lines

Acute myeloid leukemia (AML), a genetically heterogeneous disease, frequently manifests the t(8;21) translocation, a common cytogenetic anomaly. Recent studies have identified prevalent CCND2 mutations in t(8;21) AML, potentially accelerating proliferation via cell cycle deregulation. Nakatani et al. utilized selective CDK4/6 inhibitors (palbociclib and abemaciclib) on AML cell lines to assess their effects on cell cycle arrest and autophagy induction. The IC50 of CDK4/6 inhibitors was determined using 19 AML cell lines (CMK-86, Kasumi-1, SKNO-1, ML-2, HL-60, HEL, MV4-11, NB-4, KG-1a, Kasumi-6, KG-1, KO52, MOLM-16, U937, Kasumi-3, UF-1, and MOLM-13 cell lines), including two with t(8;21) (Fig. 2a). They found a moderate correlation between the IC50 values of palbociclib and abemaciclib (R² = 0.56). The t(8;21) AML cell lines showed significantly lower IC50 values for both inhibitors compared to non-t(8;21) cell lines (Fig. 2a, b). CDK4/6 inhibitors impaired proliferation in Kasumi-1 and SKNO-1 cells, indicating cell cycle arrest at the G1 phase, as shown by a reduced S/G2/M phase cell percentage (Fig. 2c-e). In shLuc- and shCCND2-transfected Kasumi-1 cells, CDK4/6 inhibitors significantly reduced proliferation, suggesting their potential efficacy in treating t(8;21) AML.

Fig. 2. CDK4/6 inhibitors induce cell cycle arrest in t(8;21) AML cell lines (Nakatani K, Matsuo H, et al., 2021).