Clinical Significance of Ck2 (CSNK2) and C-Myc Expression in Childhood Acute Lymphoblastic Leukemia

• Published in: Blood 2016-12, Vol.128 (22), p.5269-5269
• Main Authors: Bonaccorso, Paola, La Rosa, Manuela, Andriano, Nellina, Iachelli, Valeria, Cannata, Emanuela, Bellia, Francesco, Licciardello, Marinella, Di Cataldo, Andrea, Russo, Giovanna, Lo Nigro, Luca
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.5269.5269

Background. Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and a major cause of childhood cancer-related mortality. Although the cure rate now approaches 90%, certain pediatric ALL subgroups present subsequent relapse. For this reason, analyses of cell signaling pathways will help to identify new markers and/or targets for tailored therapy. PI3K/AKT/mTOR activation is frequently found in both B-ALL and T-ALL. Protein kinase Ck2 (CSNK2) activity in pediatric ALL was increased and its inhibition restored PTEN phosphatase activity with subsequent inactivation of AKT. Moreover, Ck2 may serve the activity of oncogenes such as BCR-ABL and c-MYC, control the activation of other critical signaling cascades (JAK-STAT), and sustain multiple cellular stress-elicited pathway such as the proteotoxic stress, unfolded protein and DNA-damage responses. Ck2 has also been shown to have an essential role in tuning signals derived from the stromal tumor microenvironment (Piazza F et al, Oncogene2016). Material and Methods. We analyzed cDNA collected from 46 patients with B-ALL [19 High Risk (HR) for Minimal Residual Disease (MRD) and 27 NON-HR] and 25 with T-ALL (8 HR and 17 NON-HR), respectively, diagnosed in our Center from 2000 to 2012. The latter subgroup was screened fro PTEN-Exon7 mutations and TXL3 rearrangements. We evaluated the gene expression of Ck2 and c-Myc genes using RQ-PCR with Sybr-Green and a relative quantification method (ΔΔCt method), comparing gene’s expression from patients with samples from 6 healty donors (HDs). In order to demonstrate the correlation between genetic alteration and signaling transduction, specifically in HR patients , we analyzed some phosphoproteins by Phospho-flow approach. We profiled 5 proteins (STAT3, STAT5, CREB, PTEN and pS6) in 4 T-ALL cases (3 with PTEN-Exon 7 mutation). Results. We observed a significant difference of Ck2 expression in T-ALL NON-HR patients vs HDs (Mean Ck2 Fold-Changes 3.494 vs 1.17, p=0.0315) and in T-ALL HR patients (6.384 vs 1.17, p=0.0219) vs HDs (Fig 1A and B). Comparing NON-HR vs HR cases, we found a statistically significant difference (p