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Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta-analysis

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Abstract

The Wilms’ tumor 1 (WT1) expression has been recognized in a substantial number of acute myeloid leukemia (AML) patients. Some studies indicated the association of diagnosed WT1 higher expression (WT1H) and poor outcome in the AML patients, while other studies had different opinions. Therefore, we performed a meta-analysis to evaluate the controversial prognostic significance of diagnosed WT1H in AML. Eligible studies were identified from several databases including PubMed, Embase, Web of Science, and the Cochrane Library (up to September 2014). The primary end point was overall survival (OS) and disease-free survival (DFS) was chosen as secondary end point. If possible, we would pool estimate effects (hazard ratio [HR] with 95 % confidence interval [CI]) of outcomes in both fixed and random effects models. Eleven studies, covering 1497 AML patients, were included in this meta-analysis. Pooled HRs indicated that diagnosed WT1H had a poor impact on the survival of AML patients (HR for OS, 1.37; HR for DFS, 1.38). Furthermore, diagnosed WT1H appeared to be an adverse prognostic indicator in adult AML (HR for OS, 1.43; HR for DFS, 1.41) and non-promyelocytic AML (non-M3 AML) (HR for OS, 1.46; HR for DFS, 1.41). Diagnosed WT1H had slightly but significantly poor prognostic impact on OS and DFS of patients with AML in total population and some specific subgroups.

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References

  1. Dohner H, Estey EH, Amadori S et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474

    Article  PubMed  Google Scholar 

  2. Slovak ML, Kopecky KJ, Cassileth PA et al (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96:4075–4083

    CAS  PubMed  Google Scholar 

  3. Chung SS (2014) Genetic mutations in acute myeloid leukemia that influence clinical decisions. Curr Opin Hematol 21:87–94

    Article  CAS  PubMed  Google Scholar 

  4. Lin TL, Smith BD (2011) Prognostically important molecular markers in cytogenetically normal acute myeloid leukemia. Am J Med Sci 341:404–408

    Article  PubMed Central  PubMed  Google Scholar 

  5. Bergmann L, Miething C, Maurer U et al (1997) High levels of Wilms’ tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood 90:1217–1225

    CAS  PubMed  Google Scholar 

  6. Inoue K, Sugiyama H, Ogawa H et al (1994) WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood 84:3071–3079

    CAS  PubMed  Google Scholar 

  7. Schmid D, Heinze G, Linnerth B et al (1997) Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia. Leukemia 11:639–643

    Article  CAS  PubMed  Google Scholar 

  8. Yanada M, Terakura S, Yokozawa T et al (2004) Multiplex real-time RT-PCR for prospective evaluation of WT1 and fusion gene transcripts in newly diagnosed de novo acute myeloid leukemia. Leuk Lymphoma 45:1803–1808

    Article  CAS  PubMed  Google Scholar 

  9. Hamalainen MM, Kairisto V, Juvonen V et al (2008) Wilms tumour gene 1 overexpression in bone marrow as a marker for minimal residual disease in acute myeloid leukaemia. Eur J Haematol 80:201–207

    Article  PubMed  Google Scholar 

  10. Nowakowska-Kopera A, Sacha T, Florek I et al (2009) Wilms’ tumor gene 1 expression analysis by real-time quantitative polymerase chain reaction for monitoring of minimal residual disease in acute leukemia. Leuk Lymphoma 50:1326–1332

    Article  CAS  PubMed  Google Scholar 

  11. Miglino M, Colombo N, Pica G et al (2011) WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia. Leuk Lymphoma 52:1961–1969

    Article  CAS  PubMed  Google Scholar 

  12. Miyawaki S, Hatsumi N, Tamaki T et al (2010) Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia. Leuk Lymphoma 51:1855–1861

    Article  CAS  PubMed  Google Scholar 

  13. Barragan E, Cervera J, Bolufer P et al (2004) Prognostic implications of Wilms’ tumor gene (WT1) expression in patients with de novo acute myeloid leukemia. Haematologica 89:926–933

    CAS  PubMed  Google Scholar 

  14. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta analyses .Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  15. Tierney JF, Stewart LA, Ghersi D et al (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16

    Article  PubMed Central  PubMed  Google Scholar 

  16. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  17. Higgins JPT and Green S (2011) Chapter 9: Analysing data and undertaking meta-analyses. Cochrane handbook for systematic reviews of interventions version 5.1.0

  18. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  19. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Damm F, Heuser M, Morgan M et al (2011) Integrative prognostic risk score in acute myeloid leukemia with normal karyotype. Blood 117:4561–4568

    Article  CAS  PubMed  Google Scholar 

  21. Nomdedeu JF, Hoyos M, Carricondo M et al (2013) Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML. Leukemia 27:2157–2164

    Article  CAS  PubMed  Google Scholar 

  22. Kim HJ, Choi EJ, Sohn HJ et al (2013) Combinatorial molecular marker assays of WT1, survivin, and TERT at initial diagnosis of adult acute myeloid leukemia. Eur J Haematol 91:411–422

    Article  CAS  PubMed  Google Scholar 

  23. Luo S, Yu K, Yan QX et al (2014) Analysis of WT1 mutations, expression levels and single nucleotide polymorphism rs16754 in de novo non-M3 acute myeloid leukemia. Leuk Lymphoma 55:349–357

    Article  CAS  PubMed  Google Scholar 

  24. Lyu X, Xin Y, Mi R et al (2014) Overexpression of Wilms tumor 1 gene as a negative prognostic indicator in acute myeloid leukemia. PLoS One 9:e92470

    Article  PubMed Central  PubMed  Google Scholar 

  25. Brieger J, Weidmann E, Maurer U et al (1995) The Wilms’ tumor gene is frequently expressed in acute myeloblastic leukemias and may provide a marker for residual blast cells detectable by PCR. Ann Oncol 8:811–816

    Google Scholar 

  26. Cilloni D, Gottardi E, de Micheli D et al (2002) Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring minimal residual disease in acute leukemia patients. Leukemia 16:2115–2121

    Article  CAS  PubMed  Google Scholar 

  27. Rein LA, Chao NJ (2014) WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy. Expert Opin Investig Drugs 23(3):417–426

    Article  CAS  PubMed  Google Scholar 

  28. Hou HA, Huang TC, Lin LI et al (2010) WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system. Blood 115:5222–5231

    Article  CAS  PubMed  Google Scholar 

  29. Damm F, Heuser M, Morgan M et al (2010) Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a favorable outcome in patients with cytogenetically normal acute myeloid leukemia. J Clin Oncol 28:578–585

    Article  CAS  PubMed  Google Scholar 

  30. Liersch R, Muller-Tidow C, Berdel WE et al (2014) Prognostic factors for acute myeloid leukaemia in adults—biological significance and clinical use. Br J Haematol 165:17–38

    Article  PubMed  Google Scholar 

  31. Ommen HB, Nyvold CG, Braendstrup K et al (2008) Relapse prediction in acute myeloid leukaemia patients in complete remission using WT1 as a molecular marker: development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals. Br J Haematol 141:782–791

    Article  CAS  PubMed  Google Scholar 

  32. Rossi G, Minervini MM, Melillo L et al (2014) Predictive role of minimal residual disease and log clearance in acute myeloid leukemia: a comparison between multiparameter flow cytometry and Wilm’s tumor 1 levels. Ann Hematol 93:1149–1157

    CAS  PubMed  Google Scholar 

  33. Lambert J, Lambert J, Nibourel O et al (2014) MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget 5:6280–6288

    PubMed Central  PubMed  Google Scholar 

  34. Gray JX, McMillen L, Mollee P et al (2012) WT1 expression as a marker of minimal residual disease predicts outcome in acute myeloid leukemia when measured post-consolidation. Leuk Res 36:453–458

    Article  CAS  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

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Correspondence to Qin You-wen.

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Yang Yi-ning and Wang Xiao-rui contributed equally to the article.

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Yi-ning, Y., Xiao-rui, W., Chu-xian, Z. et al. Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta-analysis. Ann Hematol 94, 929–938 (2015). https://doi.org/10.1007/s00277-014-2295-6

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  • DOI: https://doi.org/10.1007/s00277-014-2295-6

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