Current Hematologic Malignancy Reports

, Volume 4, Issue 2, pp 83–88

MicroRNA expression in acute myeloid leukemia

  • Guido Marcucci
  • Michael D. Radmacher
  • Krzysztof Mrózek
  • Clara D. Bloomfield
Article
  • 199 Downloads

Abstract

Acute myeloid leukemia (AML) is a group of diseases that are very heterogeneous with regard to cytogenetic aberrations, gene mutations, and changes in expression of numerous genes. A new class of genes known as microRNAs recently was found to be involved in myeloid leukemogenesis. These genes are transcribed into regulatory, noncoding RNAs that control mRNA and protein expression of target genes. Genome-wide analyses of microRNA expression have revealed signatures associated with selected cytogenetic and molecular subsets of AML and have led to the recognition of previously unreported molecular pathways involved in myeloid leukemogenesis. In cytogenetically normal AML, microRNA-expression profiling has also provided prognostic information in addition to that obtained from cytogenetics and analyses of gene mutations and aberrant gene expression. This article reviews recent studies that were focused on the alterations of microRNA expression in AML and their diagnostic and prognostic significance.

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References and Recommended Reading

  1. 1.
    Estey EH, Döhner H: Acute myeloid leukaemia. Lancet 2006, 368:1894–1907.PubMedCrossRefGoogle Scholar
  2. 2.
    Ries LAG, Melbert D, Krapcho M, et al. (eds): SEER Cancer Statistics Review, 1975–2005. Bethesda, MD: National Cancer Institute. Available at http://seer.cancer.gov/csr/1975_2005/.
  3. 3.
    Estey EH: Treatment of acute myeloid leukemia. Haematologica 2009, 94:10–16.PubMedCrossRefGoogle Scholar
  4. 4.
    Mrózek K, Marcucci G, Paschka P, et al.: Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: Are we ready for a prognostically prioritized molecular classification? Blood 2007, 109:431–448.PubMedCrossRefGoogle Scholar
  5. 5.
    Döner K, Döner H: Molecular characterization of acute myeloid leukemia. Haematologica 2008, 93:976–982.CrossRefGoogle Scholar
  6. 6.
    Schlenk RF, Döner K, Krauter J, et al.: Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008, 358:1909–1918.PubMedCrossRefGoogle Scholar
  7. 7.
    Arber DA, Vardiman JW, Brunning RD, et al.: Acute myeloid leukaemia with recurrent genetic abnormalities. In WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Edited by Swerdlow SH, Campo E, Harris NL, et al. Lyon: IARC Press; 2008:110–123.Google Scholar
  8. 8.
    Fröhling S, Döhner H: Chromosomal abnormalities in cancer. N Engl J Med 2008, 359:722–734.PubMedCrossRefGoogle Scholar
  9. 9.
    Mrózek K, Bloomfield CD: Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2006, 169–177.Google Scholar
  10. 10.
    Grimwade D, Walker H, Harrison G, et al.: The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998, 92:2322–2333.PubMedGoogle Scholar
  11. 11.
    Byrd JC, Mrózek K, Dodge RK, et al.: Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002, 100:4325–4336.PubMedCrossRefGoogle Scholar
  12. 12.
    Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000, 96:4075–4083.PubMedGoogle Scholar
  13. 13.
    Paschka P, Marcucci G, Ruppert AS, et al.: Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2008, 26:4595–4602.PubMedCrossRefGoogle Scholar
  14. 14.
    Virappane P, Gale R, Hills R, et al.: Mutation of the Wilms’ tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: The United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 2008, 26:5429–5435.PubMedCrossRefGoogle Scholar
  15. 15.
    Marcucci G, Maharry K, Whitman SP, et al.: High expression levels of the ETS-related gene, ERG, predict adverse outcome and improve molecular risk-based classification of cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2007, 25:3337–3343.PubMedCrossRefGoogle Scholar
  16. 16.
    Langer C, Radmacher MD, Ruppert AS, et al.: High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 2008, 111:5371–5379.PubMedCrossRefGoogle Scholar
  17. 17.
    Heuser M, Beutel G, Krauter J, et al.: High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 2006, 108:3898–3905.PubMedCrossRefGoogle Scholar
  18. 18.
    Döhner K, Schlenk RF, Habdank M, et al.: Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 2005, 106:3740–3746.PubMedCrossRefGoogle Scholar
  19. 19.
    Paschka P, Marcucci G, Ruppert AS, et al.: Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006, 24:3904–3911.PubMedCrossRefGoogle Scholar
  20. 20.
    Mrózek K, Marcucci G, Paschka P, Bloomfield CD: Advances in molecular genetics and treatment of core-binding factor acute myeloid leukemia. Curr Opin Oncol 2008, 20:711–718.PubMedCrossRefGoogle Scholar
  21. 21.
    Wouters BJ, Löwenberg B, Delwel R: A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects. Blood 2009, 113:291–298.PubMedCrossRefGoogle Scholar
  22. 22.
    Golub TR, Slonim DK, Tamayo P, et al.: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999, 286:531–537.PubMedCrossRefGoogle Scholar
  23. 23.
    Verhaak RG, Wouters BJ, Erpelinck CAJ, et al.: Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling. Haematologica 2009, 94:131–134.PubMedCrossRefGoogle Scholar
  24. 24.
    Valk PJM, Verhaak RGW, Beijen MA, et al.: Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 2004, 350:1617–1628.PubMedCrossRefGoogle Scholar
  25. 25.
    Bullinger L, Döhner K, Bair E, et al.: Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N Engl J Med 2004, 350:1605–1616.PubMedCrossRefGoogle Scholar
  26. 26.
    Radmacher MD, Marcucci G, Ruppert AS, et al.: Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study. Blood 2006, 108:1677–1683.PubMedCrossRefGoogle Scholar
  27. 27.
    Metzeler KH, Hummel M, Bloomfield CD, et al.: An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 2008, 112:4193–4201.PubMedCrossRefGoogle Scholar
  28. 28.
    Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281–297.PubMedCrossRefGoogle Scholar
  29. 29.
    Ambros V: The functions of animal microRNAs. Nature 2004, 431:350–355.PubMedCrossRefGoogle Scholar
  30. 30.
    Gregory RI, Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res 2005, 65:3509–3512.PubMedCrossRefGoogle Scholar
  31. 31.
    Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 2006, 6:857–866.PubMedCrossRefGoogle Scholar
  32. 32.
    Calin GA, Sevignani C, Dumitru CD, et al.: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004, 101:2999–3004.PubMedCrossRefGoogle Scholar
  33. 33.
    Garzon R, Croce CM: MicroRNAs in normal and malignant hematopoiesis. Curr Opin Hematol 2008, 15:352–358.PubMedCrossRefGoogle Scholar
  34. 34.
    Chang TC, Yu D, Lee YS, et al.: Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 2008, 40:43–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Mi S, Lu J, Sun M, et al.: MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci U S A 2007, 104:19971–19976.PubMedCrossRefGoogle Scholar
  36. 36.
    Li Z, Lu J, Sun M, et al.: Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci U S A 2008, 105:15535–15540.PubMedCrossRefGoogle Scholar
  37. 37.
    Dixon-McIver A, East P, Mein CA, et al.: Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS ONE 2008, 3:e2141.PubMedCrossRefGoogle Scholar
  38. 38.
    Jongen-Lavrencic M, Sun SM, Dijkstra MK, et al.: MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 2008, 111:5078–5085.PubMedCrossRefGoogle Scholar
  39. 39.
    Garzon R, Volinia S, Liu CG, et al.: MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 2008, 111:3183–3189.PubMedCrossRefGoogle Scholar
  40. 40.
    Garzon R, Garofalo M, Martelli MP, et al.: Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 2008, 105:3945–3950.PubMedCrossRefGoogle Scholar
  41. 41.
    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, 205:585–594.PubMedCrossRefGoogle Scholar
  42. 42.
    Marcucci G, Maharry K, Radmacher MD, et al.: Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B study. J Clin Oncol 2008, 26:5078–5087.PubMedCrossRefGoogle Scholar
  43. 43.
    Hackanson B, Bennett KL, Brena RM, et al.: Epigenetic modification of CCAAT/enhancer binding protein alpha expression in acute myeloid leukemia. Cancer Res 2008, 68:3142–3151.PubMedCrossRefGoogle Scholar
  44. 44.
    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, 21:912–916.PubMedGoogle Scholar
  45. 45.
    Isken F, Steffen B, Merk S, et al.: Identification of acute myeloid leukaemia associated microRNA expression patterns. Br J Haematol 2008, 140:153–161.PubMedCrossRefGoogle Scholar
  46. 46.
    Marcucci G, Radmacher MD, Maharry K, et al.: MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008, 358:1919–1928.PubMedCrossRefGoogle Scholar
  47. 47.
    Mariathasan S, Monack DM: Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 2007, 7:31–40.PubMedCrossRefGoogle Scholar
  48. 48.
    Choong ML, Yang HH, McNiece I: MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis. Exp Hematol 2007, 35:551–564.PubMedCrossRefGoogle Scholar
  49. 49.
    Baltimore D, Boldin MP, O’Connell RM, et al.: Micro-RNAs: new regulators of immune cell development and function. Nat Immunol 2008, 9:839–845.PubMedCrossRefGoogle Scholar
  50. 50.
    Taganov KD, Boldin MP, Chang K-J, 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, 103:12481–12486.PubMedCrossRefGoogle Scholar
  51. 51.
    Yang M, Mattes J: Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol Ther 2008, 117:94–104.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  • Guido Marcucci
    • 1
  • Michael D. Radmacher
  • Krzysztof Mrózek
  • Clara D. Bloomfield
  1. 1.The Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA

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