Skip to main content
SpringerLink
Log in

Evaluation of microRNA-146a expression in acute lymphoblastic leukemia

  • Research Article
  • Published:
Frontiers in Biology

Abstract

MicroRNAs (miRNAs) play an essential role in the development and progression of acute lymphoblastic leukemia (ALL), and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high (18.75%), low (27.08%) and not different (54.17%) in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes (P190 and some translocations) with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients.We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Béres N J, Szabó D, Kocsis D, Szucs D, Kiss Z, Müller K E, Lendvai G, Kiss A, Arató A, Sziksz E, Vannay Á, Szabó A J, Veres G (2016). Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis, 22(2): 327–335

    Article  PubMed  Google Scholar 

  • Bottoni A, Calin G (2013). A Calin G. MicroRNAs as main players in the pathogenesis of chronic lymphocytic leukemia. MicroRNA, 2(3): 158–164

    CAS  Google Scholar 

  • Contreras J, Palanichamy J, Tran T, Fernando T, Rodriguez-Malave N, Goswami N, Arboleda V A, Casero D, Rao D S (2015). MicroRNA-146a modulates B-cell oncogenesis by regulating Egr1. Oncotarget, 6(13): 11023–11037

    Article  PubMed  PubMed Central  Google Scholar 

  • Daschkey S, Röttgers S, Giri A, Bradtke J, Teigler-Schlegel A, Meister G, Borkhardt A, Landgraf P (2013). MicroRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways. Plos One, 8(2): 276–276

    Article  Google Scholar 

  • de Oliveira J C, Scrideli C A, Brassesco M S, Morales A G, Pezuk J A, de Paula Queiroz R, Yunes J A, Brandalise S R, Tone L G (2012). Differential miRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features. Leuk Res, 36(3): 293–298

    Article  PubMed  Google Scholar 

  • Du J, Lu C, Cui G, Chen Y, He J (2013). DNA repair gene XRCC1 polymorphisms and susceptibility to childhood acute lymphoblastic leukemia: a meta-analysis. Chin J Cancer Res, 25(4): 405–415

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duyu M, Durmaz B, Gunduz C, Vergin C,Yilmaz Karapinar D, Aksoylar S, Kavakli K, Cetingul N, Irken G, Yaman Y, Ozkinay F, Cogulu O (2014). Prospective evaluation of whole genome microRNA expression profiling in childhood acute lymphoblastic leukemia. BioMed Research International, 2014(1): 967585–967585

    PubMed  PubMed Central  Google Scholar 

  • Ebert B L (2010). Genetic deletions in AML and MDS. Best Pract Res Clin Haematol, 23(4): 457–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fallah P, Arefian E, Naderi M, Aghaee-Bakhtiari S H, Atashi A, Ahmadi K, Shafiee A, Soleimani M (2013). miR-146a and miR-150 promote the differentiation of CD133 + cells into T-lymphoid lineage. Mol Biol Rep, 40(8): 4713–4719

    Article  CAS  PubMed  Google Scholar 

  • Faraoni I, Antonetti F R, Cardone J, Bonmassar E (2009). miR-155 gene: a typical multifunctional microRNA. Biochimica et Biophysica Acta (BBA)-. Molecular Basis of Disease., 1792(6): 497–505

    Article  CAS  Google Scholar 

  • Ferreira A, Moura L, Tojal I, Ambrósio L, Pinto-Simões B, Hamerschlak N, Calin G A, Ivan C, Covas D T, Kashima S, Castro F A (2014). ApoptomiRs expression modulated by BCR–ABL is linked to CML progression and imatinib resistance. Blood Cells Mol Dis, 53(1): 47–55

    Article  CAS  PubMed  Google Scholar 

  • Friedmann AM, Weinstein H J (2000). The role of prognostic features in the treatment of childhood acute lymphoblastic leukemia. Oncologist, 5(4): 321–328

    Article  CAS  PubMed  Google Scholar 

  • Gaballa M R, Besa E C (2014). Myelodysplastic syndromes with 5q deletion: pathophysiology and role of lenalidomide. Ann Hematol, 93(5): 723–733

    Article  CAS  PubMed  Google Scholar 

  • Ghose J, Bhattacharyya N P (2015). Transcriptional regulation of microRNA-100, -146a, and -150 genes by p53 and NFkB p65/RelA in mouse striatal STHdh(Q7)/ Hdh(Q7) cells and human cervical carcinoma HeLa cells. RNA Biol, 12(4): 457–477

    Article  PubMed  PubMed Central  Google Scholar 

  • Hagag A A, Nosair N A, Ghaith FM, Elshenawy E H (2014). Prognostic value of protease activated receptor-1 in children with acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis, 6(1): e2014029

    Article  Google Scholar 

  • Han B W, Feng D D, Li Z G, Luo X Q, Zhang H, Li X J, Zhang X J, Zheng L L, Zeng CW, Lin K Y, Zhang P, Xu L, Chen Y Q (2011). A set of miRNAs that involve in the pathways of drug resistance and leukemic stem-cell differentiation is associated with the risk of relapse and glucocorticoid response in childhood ALL. Hum Mol Genet, 20(24): 4903–4915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hauptman N, Glavac D (2013). MicroRNAs and long non-coding RNAs: prospects in diagnostics and therapy of cancer. Radiol Oncol, 47(4): 311–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jurado-Camino T, Córdoba R, Esteban-Burgos L, Hernández-Jiménez E, Toledano V, Hernandez-Rivas J A, Ruiz-Sainz E, Cobo T, Siliceo M, Perez de Diego R, Belda C, Cubillos-Zapata C, Lopez-Collazo E (2015). Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance. J Immunol, 194(2): 719–727

    Article  CAS  PubMed  Google Scholar 

  • Li P, Wang X (2013). Role of signaling pathways and miRNAs in chronic lymphocytic leukemia. Chin Med J (Engl), 126(21): 4175–4182

    CAS  Google Scholar 

  • Li X, Sanda T, Look A T, Novina C D, von Boehmer H (2011). Repression of tumor suppressor miR-451 is essential for NOTCH1- induced oncogenesis in T-ALL. J Exp Med, 208(4): 663–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mavrakis K J, Van Der Meulen J, Wolfe A L, Liu X, Mets E, Taghon T, Khan A A, Setty M, Rondou P, Vandenberghe P, Delabesse E, Benoit Y, Socci N B, Leslie C S, Van Vlierberghe P, Speleman F, Wendel H G (2011). A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat Genet, 43(7): 673–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mei Y, Gao C, Wang K, Cui L, Li W, Zhao X, Liu F, Wu M, Deng G, Ding W, Jia H, Li Z (2014). Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia. Cancer Sci, 105(4): 463–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musilova K, Mraz M (2015). MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia, 29(5): 1004–1017

    Article  CAS  PubMed  Google Scholar 

  • Naderi M, Abdul T H, Soleimani M, Shabani I, Hashemi S M (2015). A Home-brew Real-time PCR Assay for Reliable Detection and Quantification of Mature miR-122. Appl Immunohistochem Mol Morphol, 23(8): 60–66

    Article  Google Scholar 

  • Portell C A, Wenzell C M, Advani A S (2013). Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol, 5: 5–11

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rosato P, Anastasiadou E, Garg N, Lenze D, Boccellato F, Vincenti S, Severa M, Coccia E M, Bigi R, Cirone M, Ferretti E, Campese A F, Hummel M, Frati L, Presutti C, Faggioni A, Trivedi P (2012). Differential regulation of miR-21 and miR-146a by Epstein–Barr virus-encoded EBNA2. Leukemia, 26(11): 2343–2352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saki N, Abroun S, Soleimani M, Mortazavi Y, Kaviani S, Arefian E (2014). The roles of miR-146a in the differentiation of Jurkat Tlymphoblasts. Hematology., 19(3): 141–147

    Article  CAS  PubMed  Google Scholar 

  • Schotte D, De Menezes R X, Moqadam F A, Khankahdani L M, Lange-Turenhout E, Chen C, Pieters P, Den Boer M L (2011) MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica, 96(5): 703–711

    Article  PubMed  PubMed Central  Google Scholar 

  • Schotte D, Lange-Turenhout E A, Stumpel D J, Stam R W, Buijs-Gladdines J G, Meijerink J P, Pieters R, Den Boer M L (2010). Expression of miR-196b is not exclusively MLL-driven but especially linked to activation of HOXA genes in pediatric acute lymphoblastic leukemia. Haematologica. 95(10): 1675–1682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • So A Y L, Zhao J L, Baltimore D (2013). The Yin and Yang of microRNAs: leukemia and immunity. Immunol Rev, 253(1): 129–145

    Article  PubMed  PubMed Central  Google Scholar 

  • Starczynowski D T, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells R A, Buckstein R, Lam W, Humphries R K, Karsan A (2010). Identification of miR-145 and miR-146a as mediators of the 5q-syndrome phenotype. Nat Med, 16(1): 49–58

    Article  CAS  PubMed  Google Scholar 

  • Visone R, Rassenti L Z, Veronese A, Taccioli C, Costinean S, Aguda B D, Volinia S, Ferracin M, Palatini J, Balatti V, Alder H, Negrini M, Kipps T J, Croce C M (2009). Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood, 114(18): 3872–3879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Li Z, He C, Wang D, Yuan X, Chen J, Jin J (2010). MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cells Mol Dis, 44(3): 191–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong Q, Yang Y, Wang H, Li J, Wang S, Li Y, Yang Y, Cai K, Ruan X, Yan J, Hu S, Fang X (2014). Characterization of miRNomes in acute and chronic myeloid leukemia cell lines. Genomics Proteomics Bioinformatics, 12(2): 79–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Jiang N, Huang G, Tay J L S, Lin B, Bi C, Koh G S, Li Z, Tan J, Chung T H, Lu Y, Ariffin H, Kham S K Y, Yeoh A E J, Chng W J (2013). Deregulated MIR335 that targets MAPK1 is implicated in poor outcome of paediatric acute lymphoblastic leukaemia. Br J Haematol, 163(1): 93–103

    Article  CAS  PubMed  Google Scholar 

  • Yin J Y, Tang Q, Qian W, Qian J, Lin J, Wen X M, Zhou J D, Zhang Y Y, Zhu X W, Deng Z Q (2014). Increased expression of miR-24 is associated with acute myeloid leukemia with t (8; 21). Int J Clin Exp Pathol, 7(11): 8032–8038

    PubMed  PubMed Central  Google Scholar 

  • Zhang H, Luo X Q, Zhang P, Huang L B, Zheng Y S, Wu J, Zhou H, Qu L H, Xu L, Chen Y Q (2009). MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia. PLoS ONE, 4(11): e7826

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Health Research Institute, Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Farzaneh Tavakoli, Kaveh Jaseb, Mohammad Ali Jalali Far, Elahe Khodadi & Najmaldin Saki

  2. Department of hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Masoud Soleimani

Authors
  1. Farzaneh Tavakoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaveh Jaseb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Ali Jalali Far
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masoud Soleimani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elahe Khodadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Najmaldin Saki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Najmaldin Saki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tavakoli, F., Jaseb, K., Far, M.A.J. et al. Evaluation of microRNA-146a expression in acute lymphoblastic leukemia. Front. Biol. 11, 53–58 (2016). https://doi.org/10.1007/s11515-016-1387-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-016-1387-1

Keywords

Search

Navigation