Circulating miR-126-3p and miR-423-5p Expression in de novo Adult Acute Myeloid Leukemia: Correlations with Response to Induction Therapy and the 2-Year Overall Survival

Abstract

Background

Acute myeloid leukemia (AML) results from sequential genetic alterations in a normal hematopoietic stem cell or its progenitors giving rise to an autonomous clone that dominates the bone marrow leading to marrow failure. MicroRNAs are short non-coding nucleic acid sequences that regulate post-transcriptional gene expression by base-pairing with their target mRNAs. MiRNAs can be secreted into extracellular fluids and carried to target cells by vesicles or bound to proteins. Intracellular and circulating miRNAs are believed to be useful markers in the diagnosis, prognosis, and treatment of various cancers. Practically, circulating miRNAs are more stable at room temperatures and extreme conditions.

Purpose

This study aimed to compare the expression of miR-126-3p and miR-423-5p in patients and normal subjects and correlate their expression with response to induction therapy and with their 2-year overall survival rate.

Patients and Methods

Circulating miR-126-3p and miR-423-5p was measured in the plasma of 43 adult AML patients and 35 age- and sex-matched controls by quantitative reverse transcriptase PCR. The fold change in differential expression for each gene was calculated using the comparative cycle threshold method.

Results

There was an increase in the expression of the studied miRNAs in patients compared to the control group. The average expression fold change of miR-126-3p was 3.02 (p= 0.010). The average expression fold change of miR-423-5p was 4.09 (p= 0.003). No significant correlation was found between the expression of miR-126-3p and miR-423-5p in the studied AML patients (r = 0.094, p = 0.22). Furthermore, no relationship was found between the expression of the studied miRNAs and response to induction therapy or the 2-year survival rate.

Conclusion

Although further studies are needed, our findings highlight the studied circulating miRNAs as possible diagnostic markers for AML.

Keywords:

• acute myeloid leukemia
• miR-126-3p
• miR-423-5p
• response to induction therapy
• overall survival
• polymerase chain reaction

Data Sharing Statement

Data related to this research paper including raw data, materials and methods, PCR curves, Spike-in control data, software and algorithms will be provided upon reasonable request.

Ethics and Consent

This research was approved by the Research Ethics Committee at the College of Medicine, University of Baghdad, Iraq. Signed informed consent was obtained from each patient in accordance with the Declaration of Helsinki. There is no material reproduced from other sources to need special permission from the copyright owner. This research does not include any clinical trial.

Acknowledgments

We are thankful to the staff of the hematology laboratory and the clinical hematology department of the Medical City complex for their cooperation in the stage of sample collection. Also, we are grateful to the staff of siParadigm Diagnostic Informatics for providing full assistance in performing PCR experiments of this work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was fully funded by Sherif A Nasr, president of siParadigm Diagnostic Informatics clinical laboratory located in New Jersey, USA, where all PCR experiments were done.