Prognostic significance of microRNA 17–92 cluster expression in Egyptian chronic lymphocytic leukemia patients

Abstract

Background Abnormal expression patterns of microRNAs (miRs) play an important role in the development and progression of malignancy. Identification of the clinical significance and prognostic value of these small molecules in chronic lymphocytic leukemia (CLL); a disease of heterogeneous biological landscape and clinical course, has always been of tremendous translational value. Aim To evaluate the prognostic value of microRNA17-92 cluster members in Egyptian CLL patients. Methods The expression levels of miR17-92 cluster members were evaluated by qRT-PCR, including miR17, miR18a, miR19a, miR19b-1, miR20a, and miR92a-1. Other investigations included serum LDH, serum β2 microglobulin (β2M), CD38 and ZAP70 expression by flow cytometry, fluorescence in situ hybridization (FISH) for 17p deletion, and imaging studies (computerized tomography (CT) scans of neck, chest, abdomen, and pelvis or PET-CT scans). Results Overexpression of all members of the miRNA17-92 cluster was detected in CLL patients compared to controls (p = < 0.001 for all miRs while p = 0.01 for miR19b-1). A significant positive correlation between Hb and miR17 and a significant negative correlation between Hb and miR19b-1 were observed (p = 0.041, 0.017 respectively). A statistically significant positive correlation between miR19b-1 expression and each of the WBCs and absolute lymphocytic count (ALC) was detected (p = 0.023, 0.022 respectively). Moreover, a statistically significant relation between miR19b-1 expression and advanced Binet stages was also found (p = 0.05). Regarding miR18a, a statistically significant positive correlation with LDH level was found (p = 0.003). We also found a significant positive correlation between miR92a-1 and β2M level (p = 0.005), as well as a significant relation between miR17 and negative CD38 expression (p = 0.034). However, no significant relationships between any of studied miRNA expression levels and 17p deletion or response to treatment were observed. Patients who expressed miR19b-1 were significantly indicated to start therapy at diagnosis (p = 0.05). The overall survival of CLL patients included in our study was 90.2% after 1 year from the time of diagnosis. Patients with high expression of miR19a had better OS than those with low expression (p = 0.04). Conclusions Overexpression of all members of the miR17-92 cluster was detected in Egyptian CLL patients. MiR18a, miR19b-1, and miR92a-1 also have an adverse prognostic value while miR17 can be considered a good prognostic marker. High expression of miR19a is associated with better OS.

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

“…Similarly, Farzadfard et al reported higher circulating miR-19a-3p in CLL patients than in healthy subjects [ 2 ]. Moreover, Khalifa et al showed significant overexpression of all miR-17∼92 cluster members in CLL patients in comparison to the control group [ 34 ]. Several studies suggest that miR-19a-3p may play an important role in the pathogenesis and progression of CLL [ 2 , 34 , 35 ].…”

Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with hepatic cirrhosis and hepatocellular carcinoma

“…Similar to our results, miR-18a was overexpressed in Egyptian patients with colonic polyps, PC, and CLL. [28][29][30][31] To the best of our knowledge, miR-18a did not correlate before to liver cirrhosis, and only its tumorigenic activity was known; however, the mechanism remains unclear. Murakmi et al proposed a panel of miRNAs to predict treatment response (IFNs) in chronic HCV infection and found that miR-18a was upregulated in the liver tissue of IFN non-responders.…”

“… 30 Khalifa et al also found that miR-18a was overexpressed in patients with chronic lymphocytic leukemia compared to controls. 31 To the best of our knowledge, ours was the first study that evaluated the expression level of miR-18a in HCC.…”

MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case–Control Study

“…In the same context, Lindberg et al elucidated that miRNA-17 was strongly upregulated in CD4+ T cells from the peripheral blood of multiple sclerosis (MS) patients (relapsing-remitting MS) and correlated with alterations in the expression of potential target genes potentiating its contribution to MS pathogenesis [ 41 ]. miRNA-17 was also overexpressed in the tissue and serum of several hematological and solid neoplasms, and its aberrant expression level was not only correlated with tumor progression and poor prognosis, but also mediated resistance to anti-cancer treatment [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. Overall, it could be argued that miRNA-17 represents a promising diagnostic biomarker and therapeutic target in various neoplastic and immune disorders.…”