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Published on: February 21, 2018
[microRNA expression in childhood acute granulocytic leukemia and its subtypes]
Xue-qun Luo1, Ling Xu, Zhi-yong Ke
1Department of Pediatrics, Sun Yat-sen University, Guangzhou, China. L-xuequn@126.com
Objective:
Recent studies have suggested that there is a close relation between microRNA and acute leukemia (AL). The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease.
Methods:
A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura (as control group) were enrolled in this study. Microarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA.
Results:
The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes (M1, M2 and M3) of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-125b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients.
Conclusions:
microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.
Insights
MicroRNA profiles can classify pediatric acute leukemia (AL) subtypes and predict prognosis. Specific microRNAs like miR-335, miR-126, and miR-125b are associated with different AL types and patient outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Context:
- Acute leukemia (AL) is a significant health concern in children.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in various diseases, including cancer.
- Previous research suggests a link between miRNA expression and acute leukemia.
Purpose:
- To investigate the role of microRNA profiles in the classification and diagnosis of pediatric acute leukemia.
- To explore the relationship between microRNA expression, disease pathogenesis, and prognosis in acute leukemia.
- To identify potential microRNA biomarkers for acute leukemia subtypes.
Summary:
- Microarray analysis revealed distinct microRNA expression profiles differentiating acute granulocytic leukemia (AGL) from acute lymphoblastic leukemia (ALL) and AGL subtypes (M1, M2, M3).
- Unsupervised hierarchical clustering identified specific miRNA up-regulations (miR-335, miR-126, miR-125b) for AGL subtypes.
- Elevated miR-126 and miR-125b expression correlated with better prognosis in M2 and M3 subtypes, associated with AML1-ETO and PML-RARα.
- miR-335 and miR-146 were upregulated in pediatric AGL, differing from adult findings.
Impact:
- MicroRNA profiles offer potential as novel biomarkers for classifying and diagnosing pediatric acute leukemia.
- Specific microRNA expression patterns may indicate different pathogenic mechanisms and prognoses in acute leukemia.
- This study highlights potential therapeutic targets and diagnostic tools for pediatric acute leukemia based on miRNA dysregulation.
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