Expression of Certain Leukemia/Lymphoma Related microRNAs and its Correlation with Prognosis in Childhood Acute Lymphoblastic Leukemia

Abstract

In spite of the improved efficacy of therapy, it still fails in 15-20 % of childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered expression of certain miRNAs (miRs) have been described in ALL with potential effect on prognosis. Presence of certain miRs (miRNA-16, -21, -24, -29b, -128b, -142-3p, -155, -223) was characterized in human lymphoma and leukemia cells by real-time PCR. Expression of miRs in pediatric ALL patients (n = 24) was measured before chemotherapy, at conventional response checkpoints and at relapse. Correlation between altered miR expression and response to prednisolone at day 8 of therapy and long term prognosis was statistically analysed. Overexpression of "oncomiR/inflammamiR"-21 - which is characteristic in different tumors-was missing in human ALL cells. However, higher expression of miR-128b and lower expression of miR-223 is generally characteristic for human ALL cell lines and ALL cells isolated from pediatric patients. Correlation was shown between miR-128b expression and prognosis, prednisolone response and survival data in childhood ALL. Expression of miR-128b and miR-223-both are leukemia specific-changed in parallel with percentage of bone marrow blasts in remission and during relapse. Therefore, we suggest that overexpression of miR-128b and downregulation of miR-223 shows a significant correlation with treatment response and prognosis in childhood ALL.

A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia

“…In both the test (p = 0.039) and validation (p = 0.037) cohorts, Mei et al [48] observed that the incidence of relapse or induction failure was higher in patients who had a lower expression of miR-210. Nemes et al [49] evaluated the expression of eight miRNAs (miR-16, miR-21, miR-24, miR-29b, miR-128b, miR-142-3p, miR-155, and miR-223) and their association with relapse and reported that overexpression of miR-128b and downregulation of miR-223 were associated with relapse.…”

Integrative Analysis of MicroRNA-Mediated Gene Signatures and Pathways Modulating White Blood Cell Count in Childhood Acute Lymphoblastic Leukemia

“…To the extent that miRNAs control the expression of protein-coding genes,18 regulate many biological pathways,15 are involved in disease prognosis,21 provide resistance to disease,22 and are predictors of relapse,23 this is a significant finding. Importantly, WBC is a well-known, strong, and independent predictor of both relapse and disease prognosis,8 which have also been associated with miRNAs 21–23. Therefore, discovery of miRNAs that are potentially involved in regulating genes modulating WBC could have significant impact in improving treatment protocols and development of novel therapeutics.…”

miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

“…Moreover, in cases of ALL, the expression pattern of specific miRNAs has been associated not only to the diagnosis but also to the prognosis and response to therapy. For example, miR-92a overexpression correlated with worse outcomes [135] while high miR-128b was associated with a better prognosis and response to corticosteroid treatments (Prednisolone) [136].…”