miRNA in MRD Testing
By Priyanka Varma
BURLINGAME, Calif.
Nov. 9th, 2022
miRNAs are noncoding RNAs containing 19-25 nucleotides, arising by cleavage from 70 to 100 nucleotide precursors, which hybridize to target mRNA and regulate their translation into proteins [1, 2]. Their deregulation can lead to development of cancer and metastasis. miRNAs can act as oncogenes or tumor suppressors. In serum or plasma, they are protected against ribonuclease degradation by being encapsulated in exosomes or microvesicles. Specific circulating miRNA profiles have been identified in the serum of patients with ovarian, colorectal, lung, prostate cancer, and several others. They present a novel form of intercellular communication or genetic exchange, by exosome mediated transfer of miRNAs between cells [3].
miRNA and their expression, both as single miRNA (miR-181a)and miRNA signature (multiple miRNAs) can be utilized to monitor the disease for Minimal Residual (MRD) testing in cancers like Acute Myeloid Leukemia [1]. Also, plasma miRNA-215 and circulating PB mononuclear cells miRNA (miR-148b)have been used as alternative biomarkers in immune surveillance and monitoring treatment response to Imatinib in Chronic Myeloid Leukemia [4]. Additionally, miR-128-3pand miR-181b-5p were found to be the circulating miRNAs which can be used as MRD biomarkers in pediatric precursor-B cell Acute Lymphoblastic Leukemia patients, as found in a study conducted on 46 preselected miRNAs in platelet-free plasma samples of these patients [5]. Circulating miR-451a levels which are typically low in Multiple Myeloma patients were shown to be a potential biomarker to monitor MRD and cancer relapse, as the typically downregulated marker in Multiple Myeloma showed an overexpression weeks before relapse of the disease while showing a downregulation in IL-6R mRNA and protein[6]. miRNA-135a-3p, miR200c, miR-216a, miR-340 are found to affect the invasiveness of ovarian cancer cells [3].
TaqMan miRNA array, bead-based miRNA-expression profiling assay, quantitative PCR (q-PCR) are some of the platforms which have been employed to detect miRNA in MRD testing [2, 4, 7].
The advantages of using miRNA in MRD testing are less invasive sampling compared to bone marrow aspirate as used otherwise [5]. The stability of miRNA is better over time versus longer, coding mRNAs along with an improved diagnostic accuracy (97%-98%) [2].
Bibliography:
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2. Marcucci G, Mrózek K, Radmacher MD, Garzon R,Bloomfield CD. The prognostic and functional role of microRNAs in acute myeloidleukemia. Blood. 2011 Jan 27;117(4):1121-9. doi: 10.1182/blood-2010-09-191312.Epub 2010 Nov 2. PMID: 21045193; PMCID: PMC3056468.
3. Rovira C, Güida MC, Cayota A. MicroRNAs and other small silencing RNAs in cancer. IUBMB Life. 2010 Dec;62(12):859-68. doi:10.1002/iub.399. PMID: 21154820.
4. Cumbo C, Anelli L, Specchia G, Albano F. Monitoring of Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia: Recent Advances. Cancer Manag Res. 2020 May 6;12:3175-3189. doi:10.2147/CMAR.S232752. PMID: 32440215; PMCID: PMC7211966.
5. Rzepiel,A., Kutszegi, N., Gézsi, A. et al. Circulating microRNAs as minimalresidual disease biomarkers in childhood acute lymphoblastic leukemia. JTransl Med 17, 372 (2019). https://doi.org/10.1186/s12967-019-2114-x
6. Zhong L, Jin X, Xu Z, Zeng M, Chen D, He Y,Zhang J, Jiang T, Chen J. Circulating miR-451a levels as a potential biomarkerto predict the prognosis of patients with multiple myeloma. Oncol Lett. 2020Nov;20(5):263. doi: 10.3892/ol.2020.12126. Epub 2020 Sep 21. PMID: 32989397;PMCID: PMC7517596.
7. Shivarov, Velizar, et al. "Patient-specificmicroRNA expression profiles as a marker for minimal residual disease in acutemyeloid leukemia." Hematology 19.1 (2014): 18-21.
