Tumor Biology

, Volume 37, Issue 8, pp 10571–10576 | Cite as

Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia

  • Menha Swellam
  • Nashwa El-Khazragy
Original Article


Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers.


MiRNA RT-PCR Childhood ALL 



Authors contributed equally.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Crazzolara R, Bendall L. Emerging treatments in acute lymphoblastic leukemia. CurrCancer DrugTargets. 2009;9:19–31.Google Scholar
  2. 2.
    Ching-Hon P, Robison L, Thomas AL. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.CrossRefGoogle Scholar
  3. 3.
    Pui CH. Recent research advances in childhood acute lymphoblastic leukemia. J Formos Med Assoc. 2010;109:777–87.CrossRefPubMedGoogle Scholar
  4. 4.
    Vitale A, Guarini A, Chiaretti S, Foa R. The changing scene of adult acute lymphoblastic leukemia. CurrOpinOncol. 2006;18:652–9.Google Scholar
  5. 5.
    Nguyen HT, Tian G, Murph MM. Molecular epigenetics in the management of ovarian cancer: are we investigating a rational clinical promise? Frontiers in Oncology, doi:  10.3389/fonc.2014.00071 , 2014
  6. 6.
    Swellam M, Abdelmaksoud MDE, Mahmoud MS, Ramadan A, Moneem WA, Hefny MM. Aberrant methylation of APC and RARb2 genes in breast cancer patients. IUBMB Life. 2015;67:61–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Fan Y, Fan J, Huang L, Ye M, Huang Z, Wang Y, et al. Increased expression of microRNA-196a predicts poor prognosis in human ovarian carcinoma. Int J ClinExpPathol. 2015;8:4132–7.Google Scholar
  8. 8.
    Li Q, Liu L, Li W. Identification of circulating microRNAs as biomarkers in diagnosis of hematologic cancers: a meta-analysis. Tumour Biol. 2014;35:10467–78.CrossRefPubMedGoogle Scholar
  9. 9.
    Cui J. MiR-16 family as potential diagnostic biomarkers for cancer: a systematic review and meta-analysis. Int J ClinExp Med. 2015;8:1703–14.Google Scholar
  10. 10.
    Oorschot AAD, Kuipers JE, Arentsen-Peters S, Schotte D, De Haas V, Trka J, et al. Differentially expressed miRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2012;58:715–21.CrossRefGoogle Scholar
  11. 11.
    Gefen N, Binder V, Zaliova M, Linka Y, Morrow M, Novosel A, et al. Hsa-mir-125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53. Leukemia. 2010;24:89–96.CrossRefPubMedGoogle Scholar
  12. 12.
    de Oliveira JC, Scrideli CA, Brassesco MS, Morales AG, Pezuk JA, QueirozRde P, et al. Differential miRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features. Leuk Res. 2012;36:293–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31:80–92.CrossRefPubMedGoogle Scholar
  14. 14.
    Yu H, Lindsay J, Feng ZP, Frankenberg S, Hu Y,Carone D, Shaw G,Pask AJ, O’NeillR, Papenfuss AT, Renfree MB. Evolution of coding and non-coding genes in HOX clusters of a marsupial. BMC Genomics 2012, doi: 10.1186/1471-2164-13-251
  15. 15.
    Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, et al. Baltimore DmiR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208(6):1189–201.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Williams AE, Perry MM, Moschos SA, Larner-Svensson HM, Lindsay M. Role of miRNA-146a in the regulation of the innate immune response and cancer. BiochemSoc Trans. 2008;36:1211–5.CrossRefGoogle Scholar
  17. 17.
    Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 2009;60:1065–75.CrossRefPubMedGoogle Scholar
  18. 18.
    Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561–77.PubMedGoogle Scholar
  19. 19.
    Dong C, Ji M, Ji C. microRNAs and their potential target genes in leukemia pathogenesis. Cancer Biol Ther. 2009;8(3):200–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang Y, Li Z, He C, Wang D, Yuan X, Chen J, et al. MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cell Mol Dis. 2010;44:191–7.CrossRefGoogle Scholar
  21. 21.
    Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, et al. Systematic comparison of microarray profiling, real-time PCR, and next generation sequencing technologies for measuring differential microRNA expression. RNA. 2010;16:991–1006.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Schotte D, Lange-Turenhout EAM, Stumpel DJPM,Stam RW, JGCAM Buijs-GladdinesJGCAM, MeijerinkJPP, Pieters R,Boer MLD. “Expression of miR-196b is not exclusively MLL-driven but is especially linked to activation of HOXA genes in pediatric acute lymphoblastic leukemia,” Haematologica. 2010; 95:1675–1682. Stam RW, JGCAM Buijs-GladdinesJGCAM, MeijerinkJPP, Pieters R,Boer MLDGoogle Scholar
  23. 23.
    Duyu M, Durmaz B, Gunduz C, Vergin C, KarapinarYD, Aksoylar S, Kavakli K, Cetingul N, Irken G, Yaman Y, Ozkinay F, Cogulu O. Prospective evaluation of whole genome microRNA expression profiling in childhood acute lymphoblastic leukemia. BioMed Research International Volume 2014, Article ID 967585, 7 pages 10.1155/2014/967585
  24. 24.
    Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103:12481–6.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Justiniano SE, Elavazhagan S, Fatehchand K, Shah P, Mehta P, Roda JM, et al. Fcγreceptor-induced soluble vascular endothelial growth factor receptor-1 (VEGFR-1) production inhibits angiogenesis and enhances efficacy of anti-tumor antibodies. J Biol Chem. 2013;288:26800–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Coskun E, von der Heide EK, Schlee EC, Kuhnl A, Gokbuget N, Hoelzer D, et al. The role of miRNA-196a and miRNA 196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia. Leukemia Res. 2011;35:208–13.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Biochemistry, Genetic Engineering and Biotechnology Research DivisionNational Research CentreGizaEgypt
  2. 2.Department of Clinical Pathology, Oncology Diagnostic Unit, Faculty of MedicineAin Shams UniversityCairoEgypt

Personalised recommendations