Distinctive MicroRNA Signature Is Associated With The Diagnosis And Prognosis Of Acute Leukemia

ObjectsMicroRNAs (miRNAs) are short single-stranded RNAs that have a potentiallyimportant role in gene regulation. As well miRNAs are of great importance inpathogenesis, diagnosis and prognosis of acute leukemia (AL). Therefore we studiedfive acute leukemia related miRNAs to explore the significance between thesemiRNAs and AL.MethodsOne hundred and seven acute myeloid leukemia (AML) (1 M0, 12 M1, 48 M2, 14 M3,13 M4, 15 M5, 3 M6 and 1 M7), 40 acute lymphocytic leukemia (ALL) (29 B-ALL,11 T-ALL), and 10 chronic myeloid leukemia (CML) with blast crisis (6 myeloid blastcrisis, 4 lymphocytic blast crisis) were enroled in this study.. Five acute leukemiarelated miRNAs: miR-128, Let-7b, miR-223, miR-181a and miR-155 expression weredetected by real-time fluorescence quantitative PCR. Expression of miRNA wasanalyzed with comparative method in Ct value. Karyotype was analyzed by theconventional R-banding techniques. Fms-like tyrosine kinase 3-intemal-tandemduplications (FLT3-ITD) mutation was detected by general PCR and FLT3-ITDpositive were defined as there was additional bands greater than 366 bp in Gelelectrophoresis.ResultsMiRNA-128 expression was significantly higher in ALL (p<0.001). However, theexpression levels of Let-7b and miR-223 in ALL were significantly lower than inAML. Compared with normal controls, miR-128 expression level was significantly higher in ALL, but there was no significant difference in AML (p= 0.9). Theexpression level of Let-7b or miR-223 in acute leukemia group was higher than that innormal control group (p<0.001). MiR-181a was quantitatively detected in 107 AMLpatients, and the expression level of miR181a in M1 or M2 patients (n=60) wassignificantly higher than that in M4 or M5 patients (n=28) (p=0.013). According tokaryotype, 84 cases of AML patients were classified into three groups named good(n=19), moderate (n=50) and poor (n=15). It was found that expression level ofmiR-181a in the good prognosis group was significantly lower than that in the poorprognosis group (p<0.01). FLT3-ITD mutation was detected in 107 cases of AMLpatients and there were 10 (9.4%) patients with mutation-positive. In the patients withnormal karyotype, positive rate of FLT3-ITD mutation was 21.9%. It was showed thatthe patients with FLT3-ITD positive had higher expression level of miR-155 than thatin the negative group (p=0.002). Compared with normal controls, the expression levelof miR-155 in FLT3-ITD mutation-positive group was significantly higher (p=0.002),while there was no difference in the negative group.ConclusionMiR-128, Let-7b, miR-223 and miR181a has a diagnosis value in acute leukemia, andmiR-181a and miR-155 are of great prognostic significance.