Diagnostic and prognostic value of plasma level of microRNA-92a in acute myeloid leukemia

DOI: 10.4236/ajmb.2014.41001   PDF   HTML     3,879 Downloads   6,971 Views   Citations


Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. Aim: To assess the plasma level of microRNA-92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on fifty AML patients as well as fifty healthy subjects as control. Conventional cytogenetics was performed on patients group only while measurement of the plasma level of miRNA-92a using TaqMan quantitative RT-PCR with miRNA-638 as endogenous reference for standardization and FLT3/ITD mutation was performed on patients and controls. Results: The differences in the ratio or relative quantitation (RQ) of plasma miRNa-92a to miRNA-638 in patients group to the control group have confirmed statistical significance. Also there was significant negative correlation between RQ of miRNA-92a and white blood count in patient group. Patients who achieved a response after induction chemotherapy had a mean RQ of miRNA-92a higher than non-responder with statistical significance. With regard to cytogenetics, favorable risk cytogenetics had meant RQ of miRNA-92a that was comparable to intermediate risk cytogenetics. While poor risk cytogenetics had a mean RQ which is significantly lower than both favorable and intermediate risk cytogenetics. Summary/Conclusions: Our data suggest the potential importance of the microRNA-92a as noninvasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.

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El-Halawani, N. , Hamed, N. , Eldafrawi, M. , Mourad, Z. , Sorour, A. and Ghallab, O. (2014) Diagnostic and prognostic value of plasma level of microRNA-92a in acute myeloid leukemia. American Journal of Molecular Biology, 4, 1-10. doi: 10.4236/ajmb.2014.41001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Tefferi, A., Thiele, J. and Vardiman, J.W. (2009) The 2008 world health organization classification system for myeloproliferative neoplasms: Order out of chaos. Cancer, 115, 3842-3847.
[2] Gregory, T.K., Wald, D., Chen, Y., Vermaat, J.M., Xiong, Y., et al. (2009) Molecular prognostic markers for adult acute myeloid leukaemia with normal cytogenetics. Journal of Hematology & Oncology, 2, 23.
[3] Suhag, V., Solomon, S. and Malkovska, V. (2005) Acute myelogenous leukemia. In: Rodgers, P. and Young, N., Eds., Bethesda Handbook of Clinical Hematology, Lippincott Williams &Wilkins, New York, 131-147.
[4] Bartel, D.P. (2009) MicroRNAs: Target recognition and regulatory functions. Cell, 136, 215-233.
[5] Marcucci, G., Radmacher, M.D., Maharry, K., Mrozek, K., Ruppert, A.S., et al. (2008) MicroRNA expression in cytogenetically normal acute myeloid leukemia. New England Journal of Medicine, 358, 1919-1928.
[6] Garzon, R., Volinia, S., Liu, C.G., Fernandez-Cymering, C., Palumbo, T., et al. (2008) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood, 111, 3183-3189.
[7] Jongen-Lavrencic, M., Sun, S.M., Dijkstra, M.K., Valk, P.J. and Lowenberg, B. (2008) MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood, 111, 5078-5085.
[8] Chen, X., Ba, Y., Ma, L., Cai, X., Yin, Y., et al. (2008) Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Research, 18, 997-1006.
[9] Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., et al. (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy Science of USA, 105, 10513-10518. http://dx.doi.org/10.1073/pnas.0804549105
[10] Chen, C.Z., Li, L., Lodish, H. and Bartel, D. (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science, 303, 83-86.
[11] Lu, J., Getz, G., Miska, E.A., et al. (2005) MicroRNA expression profiles classify human cancers. Nature, 435, 834-838. http://dx.doi.org/10.1038/nature03702
[12] Fazi, F., Rosa, A., Fatica, A., et al. (2005) A mini-circuitry comprising microRNA-223 and transcription factors NFI-A and C/EBPa regulates human granulopoiesis. Cell, 123, 819-831.
[13] Felli, N., Fontana, L., Pelosi, L., et al. (2005) Micro-RNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proceedings of the National Academy Science of USA, 102, 18081-18086.
[14] Garzon, R., Pichiorri, F., Palumbo, T., et al. (2006) MicroRNAs fingerprints during human megakaryocytopoiesis. Proceedings of the National Academy Science of USA, 103, 5078-5083.
[15] Calin, G.A., Dumitru, C.D., Shimizu, M., et al. (2002) Frequent deletions and down-regulation of micro-RNA genes miR-15 and miR-16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy Science of USA, 99, 15524-15529.
[16] Mi, S., Lu, J., Sun, M., Li, Z., Zhang, H., Neilly, M.B., Wang, Y., Qian, Z., Jin, J., Zhang, Y., Bohlander, S.K., Le Beau, M.M., Larson, R.A., Golub, T.R., Rowley, J.D. and Chen, J. (2007) MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proceedings of the National Academy Science of USA, 104, 19971-19976.
[17] Tanaka, M., Oikawa, K., Takanashi, M., Kudo, M., Ohyashiki, J., et al. (2009) Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS One, 4, e5532.
[18] Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT methods. Methods, 25, 402-408.
[19] Smith, M.A., Gurnew, J.G., et al. (1995) Cancer incidence and survival amongchildren and adolescence: United States SEERProgram 1975-1995. NIH Pub 99-4649. National Cancer Institute, SEER Program: Bethesda MD.
[20] Bennett, J.M., Catovsky, D., Dariel, M.T., Flandrin, G., Galton, D.A., Gralnick, H.R., et al. (1985) Proposed revised criteria for the classification of acute myeloid leukemia: A report of FAB cooperative group. Annals of Internal Medicine, 103, 626-629.
[21] Grimwade, D., Walker, H., Harrison, G., et al. (2001) The predictive value of hierarchical cytogenetic classification in older adults with AML: Analysis of 1065 patients entered into the UK medical research council AML 11 trial. Blood, 1, 1312-1320.
[22] Kaushansky, K., Lichtman, M., Beutler, E., Kipps, T., Seligsohn, V. and Prchal, J. (2010) Acute myelogenous leukemia in Williams hematology. 8th Edition, 89, Mc Graw Hill, 1930-1998.
[23] Whitman, S.P., Archer, K.J., Feng, L., et al. (2001) Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: A cancer and leukemia group B study. Cancer Research, 61, 7233-7239.
[24] Frohling, S., Schlenk, R.F., Breitruck, J., et al. (2002) Prognostic significance of activating FLT3 mutations in younger adults (16 to 60) with acute myeloid leukemia and normal cytogenetic: A study of AML study group. Blood, 99, 4372-4380.
[25] Lowenberg, B., Putten, W., Theobald, M., Gmuer, J., Verdonck, L.F., Sonneved, P., et al. (2003) Effect of priming with granulocyte-colony-stimulating factor on outcome of chemotherapy fot AML. New England Medcine, 349, 743-752. http://dx.doi.org/10.1056/NEJMoa025406
[26] Soloman, S. and Malkovska, V. (2005) Acute myelogenous leukemia. In: Rodgers, P. and Young, N., Eds., Bethesda Handbook of Clinical Hematology, Lippincott Williams &Wilkins, 135, 150.
[27] Cheson, B.D., Cassileth, P.A., Head, D.R., et al. (l999) Report of the national cancer institute-sponsored workshop on definitions and response in acute myeloid leukemia. Journal of Clinical Oncology, 8, 813.
[28] Farag, N. (2007) Study of NAD (P) H: Quinone oxireductase-1 gene polymorphism and cytogenetics studie in acute myeloid leukemia in correlation to treatment and prognosis. (MD) Thesis. Alexandria University.
[29] Van-Niel, G., Porto-Carreiro, I., Simoes, S. and Raposo, G. (2006) Exosomes a common pathway for a specialized function. Journal of Biochemistry, 140, 13-21.
[30] Pan, B.T. and Johnstone, R.M. (2003) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell, 33, 967-978. http://dx.doi.org/10.1016/0092-8674(83)90040-5
[31] Mears, R., Craven, R.A., Hanrahan, S., Totty, N., Upton, C., et al. (2004) Proteomicanalysis of melanoma-derived exosomes by two-dimensional polyacrylamide gelelectrophoresis and mass spectrometry. Proteomics, 4, 4019-4031. http://dx.doi.org/10.1002/pmic.200400876
[32] Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J., et al. (2007) Exosome mediated transfer of mRNAs and micro RNAs is a novel mechanism of geneticexchange between cells. Nature Cell Biology, 9, 654-659.
[33] Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., et al. (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy Science of USA, 105, 10513-10518.
[34] Morsy, M. (2012) Plasma level of micro-RNA 92a in acute myeloid leukemia patients over forty years old. (MS) Thesis on Press, Alexandria University.
[35] Valoczi, A., Hornyik, C., Varga, N., Burgyan, J., Kauppinen, S. and Havelda, Z. (2004) Sensitive and specific detection of micro RNAs by northern blot analysis using LNA-modified oligonucleotide probes. Nucleic Acids Research, 32, 175-183.
[36] Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., et al. (2005) Micro RNA expression profiles classify human cancers. Nature, 435, 834-838.
[37] Fichtlscherer, S., De-Rosa, S., Fox, H., Schwietz, T., Fischer, A., Liebetrau, C., et al. (2010) Circulating microRNAs in patients with coronary artery disease. Circulation Research, 107, 677-684.
[38] Yang, H., Schmuke, J.J., Flagg, L.M., Roberts, J.K., Allen, E.M., Ivashuta, S., et al. (2009) A novel real-time polymerase chain reaction method for high throughput quantification of small regulatory RNAs. Plant Biotechnology Journal, 7, 621-630.
[39] Wu, Q., Lu, Z., Li, H., Lu, J., Guo, L. and Ge, Q. (2011) Next-generation sequencing of micro RNAs for breast cancer detection. Journal of Biomedicine and Biotechnology, 597, 145-152.
[40] Mestdagh, P., Feys, T., Bernard, N., Guenther, S., Chen, C., Speleman, F., et al. (2008) High-throughput stemloop RT-Qpcr mi RNA expression profiling using minute amounts of input RNA. Nucleic Acids Research, 36, 143-151. http://dx.doi.org/10.1093/nar/gkn725
[41] Kozomara, A. and Griffiths-Jones, S. (2011) MiRBase: Integrating micro RNA annotation and deep-sequencing data. Nucleic Acids Research, 39, 152-157.
[42] Kang, K., Peng, X., Jun, L. and Deming, G. (2012) Identification of circulating miRNA biomarkers based on global quantitative real-time PCR profiling. Journal of Animal Science and Biotechnology, 3, 4-5.

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