Expression and clinical significance of miR-34b in children with acute leukemia / 中华实用儿科临床杂志

ABSTRACT

Objective To research the expression,methylated regulation and clinical significances of miR-34b in chidren with acute leukemia(AL).Methods The methylation status of miR-34b promoter CpG islands were detected with methylation-specific polymerase chain reaction (MSP) in patients with AL.Then the expression of miR-34b was compared,which was detected by Taqman real-time fluorescence quantitative polymerase chain reaction (qRT-PCR),between the AL patients and normal group,in order to analyze their relationship with the clinical indicators.Resuits In 8 leukemia cell lines (U937,HL-60,MV4-11,M2R,K562,Raji,CCRF,DAMI) showed methylation,the positive rate of the methyl was 100％.Thirty-one acute lymphocytic leukemia(ALL) pediatric patients were newly diagnosed,and 24 cases showed methylation,the methylation positive rate 77.42％ (24/31).Nineteen acute myeloid leukemia(AML) patients were newly diagnosed,and 8 cases showed methylation,the methylation positive rate was 42.11％ (8/19 cases).There was no methylation in the 23 cases of normal children.The relative expression levels of miR-34b in the normal group,the group of leukemia cell lines,the group of ALL pediatric patients with newly diagnosed,the AML group and the group with mixed lineage leukemia gene rearrangement MLL+ were 5.22 ± 1.15,0.03 ± 0.03,1.65 ± 0.69,0.18 ± 0.06,0.64 ± 0.34,respectively.The findings indicated that there were significant differences in the relative expression levels of miR-34b between the normal group and the group of leukemia cell lines,the ALL group,the AML group,and the MLL+ group.The relative expression and methylated level of miR-34b had no statistically difference in gender,age at diagnosis,WBC count,chromosome,fusion gene,MLL gene rearrangement,and the minimal residual disease(LDH) levels in newly diagnosed AML patients(all P ＞ 0.05).And the relative expression and methylated level of miR-34b had no statistically difference in gender,age at diagnosis,WBC count,immunophenotype,chromosome,fusion gene,MLL gene rearrangement,TEL/AML1 gene,risk stratification,the minimal residual disease (MRD) in thirty-three days and the LDH levels in newly diagnosed ALL patients(all P ＞ 0.05).But as for the response to prednisone experiment,there was a significant difference between the sensitive group and the non sensitive group(P ＜ 0.05).Conclusions The expression level of miR-34b in AL was significantly lower and it was regulated by methylation mechanism,which implies that miR-34b may play a role of a tumor suppressor gene in the pathogenesis of leukemia.MiR-34b may affect the early treatment response of ALL patients,and it may be an indicator of risk stratification and poor prognosis in pediatric ALL.