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Distinct power of bone marrow microRNA signatures and tumor suppressor genes for early detection of acute leukemia

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Abstract

Background

Acute leukemia involving lymphocytic and myeloid cells is cancer with a high mortality rate. Swift and timely diagnosis might be a potential approach to improving patient prognosis and survival. The microRNA (miRNA) signatures are emerging nowadays for their promising diagnostic potential. MiRNA levels from bone marrow can be used as prognostic biomarkers.

Methods

The current study was designed to evaluate if the microRNAs and tumor suppressor genes (TSGs) profiling of hematopoietic bone marrow could help in acute leukemia early detection. Also, we assessed the DNA methyltransferase 3A (DNMT3A) expression and its possible epigenetic effects on miRNAs plus TSGs expression levels. The expression levels of ten miRNAs and four TSGs involved in acute lymphocytic leukemia (ALL) as well as acute myeloid leukemia (AML) were quantified in 43 and 40 bone marrow samples of ALL and AML patients in comparison with cancer-free subjects via real-time quantitative PCR (RT-qPCR). The receiver-operating-characteristic (ROC) analysis of miRNAs was performed in the study groups. Further, the correlation between the DNMT3A and TSGs was calculated.

Results

Significant differences were detected in the bone marrow expression of miRNAs and TSGs (P < 0.05) between acute leukemia patients and healthy group. ROC analysis confirmed the ability of miR-30a, miR-101, miR-132, miR-129, miR-124, and miR-143 to discriminate both ALL and AML patients with an area under the ROC curve of ≥ 0.80 (P < 0.001) and high accuracy. The correlation between DNMT3A and P15/P16 TSGs revealed that DNMT3A plays a vital role in epigenetic control of TSGs expression. Our findings indicated that the downregulation of bone marrow miRNAs and TSGs was accompanied by acute leukemia development.

Conclusions

The authors conclude that this study could contribute to introducing useful biomarkers for acute leukemia diagnosis.

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Funding

This work was financially supported by the Tabriz University of Medical Sciences (No: IR.TBZMED.VCR.REC.13 97.019).

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Memari, Nasrin Mohajeri, Effat Alizadeh & Nosratollah Zarghami

  2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Memari

  3. Department of Stem Cells and Regenerative Medicine, Faculty of Medicine Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Vahid Tavakolpour

  4. Medical Science Branch, Islamic Azad University of Tehran, Tehran, Iran

    Behzad Poopak

  5. Checkup Clinical and Specialty Laboratory, Karaj, Iran

    Parviz Fallah

  6. Stem Cell Technology Research Center, P.O. Box: 15856-36473, 15856-36473, Tehran, Iran

    Vahid Tavakolpour & Fatemeh Kouhkan

  7. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, 51666-14766, Tabriz, Iran

    Nosratollah Zarghami

  8. Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey

    Nosratollah Zarghami

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  1. Fatemeh Memari
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Contributions

All authors contributed to the study conception and design. Material preparation, collection of biological samples, and data analysis were performed by FM, VT, BP, and PF. The first graph and revised manuscript were written by NM. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Fatemeh Kouhkan or Nosratollah Zarghami.

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The authors declare no competing interests.

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The study was approved by the research ethical committee of TUOMS.

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Informed consent was obtained by all patients in Payvand Laboratory, Tehran, Iran.

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Memari, F., Tavakolpour, V., Mohajeri, N. et al. Distinct power of bone marrow microRNA signatures and tumor suppressor genes for early detection of acute leukemia. Clin Transl Oncol 24, 1372–1380 (2022). https://doi.org/10.1007/s12094-022-02781-3

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