Best Practice & Research Clinical Haematology
Volume 22, Issue 2 , Pages 169-180 , June 2009

Gene expression profiling in acute myeloid leukaemia (AML)

  • Ulrike Bacher, MD (Doctor)

      Affiliations

    • Department of Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Hamburg, Germany
    • ,
  • Alexander Kohlmann, PhD (Molecular Biologist)

      Affiliations

    • MLL Munich Leukemia Laboratory, Munich, Germany
    • ,
  • Claudia Haferlach, MD (Doctor)

      Affiliations

    • MLL Munich Leukemia Laboratory, Munich, Germany
    • ,
  • Torsten Haferlach, MD (Professor of Medicine)

      Affiliations

    • MLL Munich Leukemia Laboratory, Munich, Germany
    • Corresponding Author InformationCorrespondence to: Torsten Haferlach, MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany. Tel.: +49 89 99017 100; Fax: +49 89 99017 109.
    web address

References 

  1. Marcucci G, Mrozek K, Bloomfield CD. Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Curr Opin Hematol. 2005;12:68–75
  2. Tallman MS. New agents for the treatment of acute myeloid leukemia. Best Pract Res Clin Haematol. 2006;19:311–320
  3. Illmer T, Ehninger G. FLT3 kinase inhibitors in the management of acute myeloid leukemia. Clin Lymphoma Myeloma. 2007;8(Suppl. 1):S24–S34
  4. Meijer E, Cornelissen JJ. Allogeneic stem cell transplantation in acute myeloid leukemia in first or subsequent remission: weighing prognostic markers predicting relapse and risk factors for non-relapse mortality. Semin Oncol. 2008;35:449–457
  5. Dohner 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
  6. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–266
  7. Falini B, Nicoletti I, Martelli MF, et al. Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. Blood. 2007;109:874–885
  8. Wouters BJ, Lowenberg B, Delwel R. A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects. Blood 2009;113:291–8.
  9. 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
  10. Bullinger L, Dohner 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
  11. 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
  12. Raponi M, Lancet JE, Fan H, et al. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia. Blood. 2008;111:2589–2596
  13. Kohlmann A, Schoch C, Dugas M, et al. Pattern robustness of diagnostic gene expression signatures in leukemia. Genes Chromosomes Cancer. 2005;42:299–307
  14. Kornblau SM, Tibes R, Qiu Y, et al. Functional proteomic profiling of AML predicts response and survival. Blood 2009;113:154–64.
  15. Suela J, Alvarez S, Cigudosa JC. DNA profiling by arrayCGH in acute myeloid leukemia and myelodysplastic syndromes. Cytogenet Genome Res. 2007;118:304–309
  16. Marcucci G, Radmacher MD, Maharry K, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1919–1928
  17. Kohlmann A, Haschke-Becher E, Wimmer B, et al. Intraplatform reproducibility and technical precision of gene expression profiling in 4 laboratories investigating 160 leukemia samples: the DACH study. Clin Chem. 2008;54:1705–1715
  18. Schoch C, Kohlmann A, Schnittger S, et al. Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles. Proc Natl Acad Sci U S A. 2002;99:10008–10013
  19. Debernardi S, Lillington DM, Chaplin T, et al. Genome-wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation-mediated fusion events. Genes Chromosomes Cancer. 2003;37:149–158
  20. Verhaak RG, Wouters BJ, Erpelinck CA, et al. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling. Haematologica 2009;94:131–4.
  21. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41–47
  22. Kohlmann A, Schoch C, Dugas M, et al. New insights into MLL gene rearranged acute leukemias using gene expression profiling: shared pathways, lineage commitment, and partner genes. Leukemia. 2005;19:953–964
  23. Haferlach T, Kohlmann A, Schnittger S, et al. AML M3 and AML M3 variant each have a distinct gene expression signature but also share patterns different from other genetically defined AML subtypes. Genes Chromosomes Cancer. 2005;43:113–127
  24. Camos M, Esteve J, Jares P, et al. Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res. 2006;66:6947–6954
  25. Murati A, Gervais C, Carbuccia N, et al. Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia 2009;23:85–94.
  26. Virtaneva K, Wright FA, Tanner SM, et al. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci U S A. 2001;98:1124–1129
  27. Schoch C, Kohlmann A, Dugas M, et al. Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q. Leukemia. 2005;19:1224–1228
  28. Schoch C, Haferlach T, Bursch S, et al. Loss of genetic material is more common than gain in acute myeloid leukemia with complex aberrant karyotype: a detailed analysis of 125 cases using conventional chromosome analysis and fluorescence in situ hybridization including 24-color FISH. Genes Chromosomes Cancer. 2002;35:20–29
  29. Schoch C, Kern W, Kohlmann A, et al. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosomes Cancer. 2005;43:227–238
  30. Lindvall C, Furge K, Bjorkholm M, et al. Combined genetic and transcriptional profiling of acute myeloid leukemia with normal and complex karyotypes. Haematologica. 2004;89:1072–1081
  31. Verhaak RG, Goudswaard CS, van PW, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood. 2005;106:3747–3754
  32. Alcalay M, Tiacci E, Bergomas R, et al. Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance. Blood. 2005;106:899–902
  33. Wilson CS, Davidson GS, Martin SB, et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood. 2006;108:685–696
  34. Mullighan CG, Kennedy A, Zhou X, et al. Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias. Leukemia. 2007;21:2000–2009
  35. Neben K, Schnittger S, Brors B, et al. Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotype. Oncogene. 2005;24:1580–1588
  36. Whitman SP, Ruppert AS, Radmacher MD, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111:1552–1559
  37. Lacayo NJ, Meshinchi S, Kinnunen P, et al. Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes. Blood. 2004;104:2646–2654
  38. Bullinger L, Dohner K, Kranz R, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML. Blood. 2008;111:4490–4495
  39. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350:1617–1628
  40. 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
  41. Wouters BJ, Jorda MA, Keeshan K, et al. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood. 2007;110:3706–3714
  42. Marcucci G, Baldus CD, Ruppert AS, et al. Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol. 2005;23:9234–9242
  43. Bullinger L, Rucker FG, Kurz S, et al. Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia. Blood. 2007;110:1291–1300
  44. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107:3463–3468
  45. Bourquin JP, Subramanian A, Langebrake C, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proc Natl Acad Sci U S A. 2006;103:3339–3344
  46. Andreeff M, Ruvolo V, Gadgil S, et al. HOX expression patterns identify a common signature for favorable AML. Leukemia 2008;22:2041–7.
  47. Raghavan M, Smith LL, Lillington DM, et al. Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia. Blood. 2008;112:814–821
  48. Gupta M, Raghavan M, Gale RE, et al. Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia. Genes Chromosomes Cancer. 2008;47:729–739
  49. Gondek LP, Tiu R, O'Keefe CL, et al. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood. 2008;111:1534–1542
  50. Suela J, Alvarez S, Cifuentes F, et al. DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups. Leukemia. 2007;21:1224–1231
  51. Garzon R, Volinia S, Liu CG, et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 2008;111:3183–3189
  52. 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
  53. Heuser M, Wingen LU, Steinemann D, et al. Gene-expression profiles and their association with drug resistance in adult acute myeloid leukemia. Haematologica. 2005;90:1484–1492
  54. 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
  55. Steinbach D, Schramm A, Eggert A, et al. Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia. Clin Cancer Res. 2006;12:2434–2441
  56. Willman CL. Has gene expression profiling improved diagnosis, classification, and outcome prediction in AML?. Best Pract Res Clin Haematol. 2008;21:21–28
  57. Haferlach T, Kohlmann A, Schnittger S, et al. Global approach to the diagnosis of leukemia using gene expression profiling. Blood. 2005;106:1189–1198
  58. Baldus CD, Bullinger L. Gene expression with prognostic implications in cytogenetically normal acute myeloid leukemia. Semin Oncol. 2008;35:356–364
  59. Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909–1918
  60. Stapnes C, Ryningen A, Hatfield K, et al. Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors. Int J Oncol. 2007;31:1529–1538
  61. Haferlach T. Molecular genetic pathways as therapeutic targets in acute myeloid leukemia. ASH, Hematology AM Soc Hematol Educ Program, 2008;400–11.
  62. Kohlmann A, Kipps TJ, Rassenti LZ, et al. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in Leukemia study prephase. Br J Haematol. 2008;142:802–807

PII: S1521-6926(09)00024-3

doi: 10.1016/j.beha.2009.04.003

Best Practice & Research Clinical Haematology
Volume 22, Issue 2 , Pages 169-180 , June 2009

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