Methyltransferase-like 3 gene expression and prognostic impact in acute myeloid leukemia patients

Background DNA methylation is involved in pathogenesis of acute myeloid leukemia (AML). N6-methyladenosine (m6A) modification of mRNA, mediated by methyltransferase-like 3 (METTL3), is one of the well-identified mRNA modifiers associated with the pathogenesis of AML. High level of METTL3 mRNA is det...

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Bibliographic Details
Published in:Egyptian Journal of Medical Human Genetics 2022-03, Vol.23 (1), p.34-13
Main Authors: Nagy, Reham Mohamed, Mohamed, Amal Abd El Hamid, El-Gamal, Rasha Abd El-Rahman, Ibrahim, Shereen Abdel Monem, Pessar, Shaimaa Abdelmalik
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
AML
Analysis
Cancer
Chemotherapy
DNA methylation
Epigenetics
Ethylenediaminetetraacetic acid
Gene expression
Genes
Genetic aspects
Genetic research
Induction therapy
Leukemia
Medical prognosis
Messenger RNA
Methylation
Methyltransferase
Methyltransferases
METTL3
N6-methyladenosine
Pathogenesis
Remission
Remission (Medicine)
Reverse transcription
RNA modification
Statistical analysis
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Summary:Background DNA methylation is involved in pathogenesis of acute myeloid leukemia (AML). N6-methyladenosine (m6A) modification of mRNA, mediated by methyltransferase-like 3 (METTL3), is one of the well-identified mRNA modifiers associated with the pathogenesis of AML. High level of METTL3 mRNA is detected in AML cells, thus can be a potential target therapy for AML. This is a preliminary study that aimed at measuring METTL3 mRNA expression level in de novo AML patients and correlating it with clinicopathological, laboratory and prognostic markers. METTL3 expression was analyzed by quantitative reverse transcription polymerase chain reaction in 40 newly diagnosed AML adults and was re-measured in the 2nd month of chemotherapy. Patients were followed up for periods up to 6 months post-induction therapy. Results METTL3 expression was found to be significantly upregulated in AML patients compared to control subjects (p < 0.001). METTL3 gene was significantly expressed among non-responders compared to responders (p < 0.001). A cutoff value was assigned for normalized METTL3 values to categorize AML patients according to response to therapy. Statistically significant association was observed between high pretreatment normalized METTL3 gene level and failure to attain complete remission at 2nd, 4th and 6th month following therapy (p = 0.01, 0.02 and 0.003, respectively). However, insignificant correlation was found between pretreatment normalized METTL3 gene level and event free survival or clinicopathological prognostic factors. Conclusion METTL3 is overexpressed in AML patients and is associated with adverse prognostic effect and failure to attain hematological remission within 6 months post-induction therapy.
ISSN:1110-8630
2090-2441
DOI:10.1186/s43042-022-00242-8