Abstract
BackgroundAbnormal 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.AimTo evaluate the prognostic value of microRNA17-92 cluster members in Egyptian CLL patients.MethodsThe 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).ResultsOverexpression 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).ConclusionsOverexpression 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.
Highlights
Abnormal expression patterns of microRNAs play an important role in the development and progression of malignancy
Overexpression of all members of the miR17-92 cluster was detected in Egyptian Chronic lymphocytic leukemia (CLL) patients
High expression of miR19a is associated with better Overall survival (OS)
Summary
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. Chronic lymphocytic leukemia (CLL) is a malignancy characterized by clonal proliferation and accumulation of mature, CD5 positive B lymphocytes in the blood, marrow, and secondary lymphoid tissues [1]. The wellestablished prognostic biomarkers in CLL include host factors (i.e., gender and age), disease markers [i.e., lymph node involvement (size, site), hepatomegaly, splenomegaly, lymphocyte doubling time (LDT), WBC count, absolute lymphocytic count (ALC), anemia, thrombocytopenia, Rai and Binet staging], antigen expression (i.e., CD38, ZAP70, and CD49d/VLA-4), serology (i.e., LDH, β2M, thymidine kinase, and IL-8), genetics (i.e., del 17p and TP53 gene mutation, del 11q, del 13q, trisomy 12, complex karyotype), epigenetics (DNA methylation), molecular markers (NOTCH1 mutation, ATM, SF3B1 mutation, BIRC3 mutation, BRAF mutation), and immunogenetics (i.e., IGHV gene mutational status and BCR structure) [5]
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