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Differentially expressed miRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukemia
Astrid A Danen-van Oorschot1, Jenny E Kuipers, Susan Arentsen-Peters
1Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Background:
miRNAs regulate gene expression, and thus play an important role in critical cellular processes. Aberrant miRNA expression patterns have been found in various types of cancer. So far, information about the expression of miRNAs in pediatric acute myeloid leukemia is limited.
Procedure:
We studied expression of miR-29a, -155, -196a, and -196b by stem-loop based RT-qPCR in 82 pediatric acute myeloid leukemia patients selected to represent relevant cytogenetic and molecular subgroups.
Results:
High miR-196a and -b expression was observed in patients carrying MLL gene rearrangements (P < 0.001), NPM1 mutations (P < 0.001), or FLT3-ITD in a cytogenetically normal background (P ≤ 0.02), compared to all other patients. In contrast, CEBPA mutated cases had a low expression of miR-196a and -b (P ≤ 0.001). Expression of miR-196a and -b was correlated with expression of neighboring HOXA and HOXB genes (Spearman's r = 0.46-0.82, P < 0.01). Expression of miR-155 was not related to cytogenetic features but high expression of miR-155 was observed in FLT3-ITD (P = 0.001) and NPM1-mutated cases (P = 0.04). Lower miR-29a expression was mainly observed in MLL-rearranged pediatric acute myeloid leukemia, specifically in cases carrying t(10;11) (P < 0.001).
Conclusions:
We show aberrant expression of specific miRNAs in clinically relevant cytogenetic and molecular subgroups of pediatric acute myeloid leukemia, suggesting a role for these miRNAs in the underlying biology in these specific subgroups.
Insights
Specific microRNAs (miRNAs) show altered expression in pediatric acute myeloid leukemia (AML) subgroups. These findings suggest miRNAs play a role in the biology of pediatric AML.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, crucial for cellular processes.
- Dysregulated miRNA expression is implicated in various cancers.
- Limited data exists on miRNA expression in pediatric acute myeloid leukemia (AML).
Purpose of the Study:
- To investigate the expression of specific miRNAs (miR-29a, -155, -196a, -196b) in pediatric AML.
- To correlate miRNA expression with cytogenetic and molecular subgroups of pediatric AML.
Main Methods:
- Stem-loop based RT-qPCR was used to analyze miRNA expression.
- 82 pediatric AML patients representing diverse subgroups were studied.
Main Results:
- High miR-196a/b expression correlated with MLL rearrangements, NPM1 mutations, and FLT3-ITD.
- Low miR-196a/b expression was observed in CEBPA mutated cases.
- miR-155 expression was elevated in FLT3-ITD and NPM1-mutated cases.
- Lower miR-29a expression was noted in MLL-rearranged pediatric AML.
Conclusions:
- Aberrant expression of specific miRNAs is evident in clinically relevant pediatric AML subgroups.
- These findings suggest a role for these miRNAs in the specific biology of pediatric AML subgroups.
