Distinctive microRNA signature is associated with the diagnosis and prognosis of acute leukemia

Abstract

MicroRNAs (miRNAs) are of great importance in pathogenesis, diagnosis and prognosis of acute leukemia (AL). We studied five AL-related miRNAs to confirm the significance of these miRNAs in AL. Samples tested included acute myeloid leukemia (AML), 107 cases; acute lymphoblastic leukemia (ALL), 40 cases. Five AL-related miRNAs: miR-128, let-7b, miR-223, miR-181a and miR-155 expression were detected by qRT-PCR. Analysis showed that miRNA-128 expression was significantly higher in ALL (P<0.001). However, the let-7b and miR-223 expressions in ALL were significantly lower than in AML (P<0.001). Compared with normal controls, miR-128 expression was significantly higher in ALL (P<0.001), but there was no significant difference in AML (P=0.900). The expressions of Let-7b and miR-223 in AL group were higher than in normal controls (P<0.001). MiR-181a was quantitatively detected in 107 AML patients, and we found that the expression of miR181a in M1 or M2 patients was significantly higher compared with it in M4 or M5 (P=0.013). According to karyotype, 84 cases of AML were classified into three groups named favorable, moderate and poor. It was found that the expression of miR-181a in favorable prognosis group was significantly lower than in poor prognosis group (P=0.015). In FLT3-ITD mutation positive patients, the miR-155 expression was significantly higher than in the negative group (P=0.002). These results support that miR-128, let-7b, miR-223 and miR181a have a diagnosis value in AL, while miR-181a and miR-155 are of great prognostic significance in AML.

MicroRNA Profiling in Chemoresistant and Chemosensitive Acute Myeloid Leukemia

“…Earlier studies on AML have indicated changes in miRNA expression associated with outcome, such as miR-181a, miR181b, miR-124, miR-128-1, miR-194, miR-219-5p, miR-220a, miR-320, and miR-155 [Marcucci et al, 2008;Li et al, 2012;Zhu et al, 2012]. None of these miRNAs, however, existed in our study.…”

MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia

“…Previous studies have shown that miR-128(-3p) acts as an oncogene in malignancies such as acute leukemia, 24,25 breast cancer 13,[26][27][28] and lung cancer. 14 However, this miRNA has also been described to have tumor suppressive functions in other cancer entities (for an overview, refer to Online Supplementary Table S4).…”

“…Other studies reported in literature support a possible oncogenic function for miR-128-3p in ALL, as miR-128(-3p) was found to be significantly more highly expressed in ALL samples than in acute myeloid leukemia samples and normal control samples. 24,25,29 Possible mechanisms that could underlie miR-128-3p over-expression in T-ALL remain to be explored in further detail. Although to the best of our knowledge chromosomal aberrations or mutations specifically affecting miR-128 loci have not been reported so far, there is evidence that miR-128-3p expression could be affected by perturbed epigenetic regulation [hypomethylation of miR-128 promoter(s)] in T-ALL cells.…”

Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (Review)

“…It was found that the expression of miRNA-181a in favorable prognosis group was significantly lower than in poor prognosis group. In FLT3-ITD mutation positive patients, the miRNA-155 expression was significantly higher than in the negative group (182). At this time only few studies have been performed on circulating miRNA in AL, but a recent study found that plasma levels of miRNA-92 might be a biomarker for acute myeloid leukemia (183).…”