Medical Oncology

, Volume 29, Issue 4, pp 2323–2331 | Cite as

Distinctive microRNA signature is associated with the diagnosis and prognosis of acute leukemia

  • Yuan-Dong Zhu
  • Li Wang
  • Chao Sun
  • Lei Fan
  • Dan-Xia Zhu
  • Cheng Fang
  • Yin-Hua Wang
  • Zhi-Jian Zou
  • Su-Jiang Zhang
  • Jian-Yong Li
  • Wei XuEmail author
Original Paper


MicroRNAs (miRNAs) are of great importance in pathogenesis, diagnosis and prognosis of acute leukemia (AL). We studied five AL-related miRNAs to confirm the significance of these miRNAs in AL. Samples tested included acute myeloid leukemia (AML), 107 cases; acute lymphoblastic leukemia (ALL), 40 cases. Five AL-related miRNAs: miR-128, let-7b, miR-223, miR-181a and miR-155 expression were detected by qRT-PCR. Analysis showed that miRNA-128 expression was significantly higher in ALL (P < 0.001). However, the let-7b and miR-223 expressions in ALL were significantly lower than in AML (P < 0.001). Compared with normal controls, miR-128 expression was significantly higher in ALL (P < 0.001), but there was no significant difference in AML (P = 0.900). The expressions of Let-7b and miR-223 in AL group were higher than in normal controls (P < 0.001). MiR-181a was quantitatively detected in 107 AML patients, and we found that the expression of miR181a in M1 or M2 patients was significantly higher compared with it in M4 or M5 (P = 0.013). According to karyotype, 84 cases of AML were classified into three groups named favorable, moderate and poor. It was found that the expression of miR-181a in favorable prognosis group was significantly lower than in poor prognosis group (P = 0.015). In FLT3-ITD mutation positive patients, the miR-155 expression was significantly higher than in the negative group (P = 0.002). These results support that miR-128, let-7b, miR-223 and miR181a have a diagnosis value in AL, while miR-181a and miR-155 are of great prognostic significance in AML.


Acute leukemia miRNA qRT-PCR Karyotype FLT3-ITD mutation 



This study was supported by National Natural Science Foundation of China (30871104, 30971296, 81170488), Natural Science Foundation of Jiangsu Province (BK2010584), Key Projects of Health Department of Jiangsu Province (K201108), University Doctoral Foundation of the Ministry of Education of China (20093234110010), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Slezak-Prochazka I, Durmus S, Kroesen BJ, et al. MicroRNAs, macrocontrol: regulation of miRNA processing. RNA. 2010;16(6):1087–95.PubMedCrossRefGoogle Scholar
  2. 2.
    Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.PubMedCrossRefGoogle Scholar
  3. 3.
    Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56.PubMedCrossRefGoogle Scholar
  4. 4.
    Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297:1901–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Munker R, Calin GA. MicroRNA profiling in cancer. Clin Sci (Lond). 2011;121(4):141–158.Google Scholar
  6. 6.
    Bissels U, Bosio A, Wagner W. MicroRNAs are shaping the hematopoietic landscape. Haematologica. 2011 [Epub ahead of print].Google Scholar
  7. 7.
    Paolini S, Gazzola A, Sabattini E, et al. Pathobiology of acute lymphoblastic leukemia. Semin Diagn Pathol. 2011;28(2):124–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Hong WJ, Medeiros BC. Unfavorable-risk cytogenetics in acute myeloid leukemia. Hematol Expert Rev. 2011;4(2):173–184.Google Scholar
  10. 10.
    De Jonge HJ, Huls G, De Bont ES. Gene expression profiling in acute myeloid leukemia. Neth J Med. 2011;69(4):167–76.PubMedGoogle Scholar
  11. 11.
    Wieser R, Scheideler M, Hackl H, et al. microRNAs in acute myeloid leukemia: expression patterns, correlations with genetic and clinical parameters, and prognostic significance. Genes Chromosomes Cancer. 2010;49(3):193–203.PubMedGoogle Scholar
  12. 12.
    Ferrara F, Palmieri S, Leoni F. Clinically useful prognostic factors in acute myeloid leukemia. Crit Rev Oncol Hematol. 2008;66(3):181–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Odenike O, Thirman MJ, Artz AS, et al. Gene mutations, epigenetic dysregulation, and personalized therapy in myeloid neoplasia: are we there yet? Semin Oncol. 2011;38(2):196–214.PubMedCrossRefGoogle Scholar
  14. 14.
    Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press; 2008.Google Scholar
  15. 15.
    Zhu DX, Miao KR, Fang C, Zhu W, Fan L, Zhu HY, Zhuang Y, Hong M, Liu P, Xu W, Li JY. Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia. Leuk Res. 2011;35(6):730–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Shaffer LG, Tommerup N, editors. ISCN 2005: an international system for human cytogenetic nomenclature. Basel: S. Karger; 2005.Google Scholar
  17. 17.
    Xu W, Zhou HF, Fan L, Qian SX, Chen LJ, Qiu HR, Zhang SJ, Li JY. Trisomy 22 as the sole abnormality is an important marker for the diagnosis of acute myeloid leukemia with inversion 16. Onkologie. 2008;31(8–9):440–4.PubMedGoogle Scholar
  18. 18.
    Qiao C, Zhang SJ, Chen LJ, Miao KR, Zhang JF, Wu YJ, Qiu HR, Li JY. Identification of the STAT5B-RARα fusion transcript in an acute promyelocytic leukemia patient without FLT3, NPM1, c-Kit and C/EBPα mutation. Eur J Haematol. 2011;86(5):442–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Debernardi S, Skoulakis S, Molloy G, et al. MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia. 2007;21(5):912–6.PubMedGoogle Scholar
  20. 20.
    Mi S, Lu J, Sun M, et al. MiRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 2007;104(50):19971–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Georgantas RW 3rd, Hildreth R, Morisot S, et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA. 2007;104(8):2750–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Fazi F, Racanicchi S, Zardo G, et al. Epigenetic silencing of the myelopoiesis regulator miRNA-223 by the AML1/ETO oncoprotein. Cancer Cell. 2007;12:457–66.PubMedCrossRefGoogle Scholar
  23. 23.
    Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451(7182):1125–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Myatt SS, Wang J, Monteiro LJ, et al. Definition of miRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 2010;70(1):367–77.PubMedCrossRefGoogle Scholar
  25. 25.
    Shell S, Park SM, Radjabi AR, et al. Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci U S A. 2007;104:11400–11405.47.Google Scholar
  26. 26.
    Lee YS, Dutta A. The tumor suppressor miRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21:1025–1103.Google Scholar
  27. 27.
    Larson RA. Micro-RNAs and copy number changes: new levels of gene regulation in acute myeloid leukemia. Chem Biol Interact. 2010;184(1–2):21–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Marcucci G, Radmacher MD, Mrózek K, et al. MicroRNA expression in acute myeloid leukemia. Curr Hematol Malig Rep. 2009;4(2):83–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Stone RM. Prognostic factors in AML in relation to (ab)normal karyotype. Best Pract Res Clin Haematol. 2009;22(4):523–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Tili E, Croce CM, Michaille JJ. miR-155: on the crosstalk between inflammation and cancer. Int Rev Immunol. 2009;28(5):264–84.PubMedCrossRefGoogle Scholar
  31. 31.
    O’Connell RM, Rao DS, Chaudhuri AA, et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med. 2008;205(3):585–94.PubMedCrossRefGoogle Scholar
  32. 32.
    Garzon R, Volinia S, Liu C, et al. MiRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 2008;111:3183–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Iguchi H, Ochiya T. Application of microRNAs to cancer therapy. Gan To Kagaku Ryoho. 2010;37(3):389–95.PubMedGoogle Scholar
  34. 34.
    Ortiz-Quintero B. RNA interference: from origins to a novel tool for gene silencing. Rev Invest Clin. 2009;61(5):412–27.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yuan-Dong Zhu
    • 1
    • 2
  • Li Wang
    • 1
  • Chao Sun
    • 1
    • 3
  • Lei Fan
    • 1
  • Dan-Xia Zhu
    • 1
  • Cheng Fang
    • 1
  • Yin-Hua Wang
    • 1
  • Zhi-Jian Zou
    • 1
  • Su-Jiang Zhang
    • 1
  • Jian-Yong Li
    • 1
  • Wei Xu
    • 1
    Email author
  1. 1.Department of Hematology, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingChina
  2. 2.Department of HematologyThe First Hospital of ChangzhouChangzhouChina
  3. 3.Department of HematologyThe Wuxi People’s HospitalWuxiChina

Personalised recommendations