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Clinical usefulness of WT1 mRNA expression in bone marrow detected by a new WT1 mRNA assay kit for monitoring acute myeloid leukemia: a comparison with expression of WT1 mRNA in peripheral blood

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Abstract

We have previously shown the clinical usefulness of Wilms’ tumor 1 gene (WT1) mRNA expression in peripheral blood (PB) as a minimal residual disease (MRD) monitoring marker in 191 acute myeloid leukemia (AML) patients using the WT1 mRNA assay kit “Otsuka” (Otsuka Pharmaceutical Co., Ltd.; “former kit”). In contrast, the usefulness of WT1 mRNA expression in bone marrow (BM) has been investigated in only a limited number of subjects using former kit. Following that previous study, a next-generation kit, WT1 mRNA assay kit II “Otsuka” (Otsuka Pharmaceutical Co., Ltd.; “new kit”) has been newly developed. In the present study, we aimed to evaluate the performance of the new kit and to investigate the clinical usefulness of WT1 mRNA expression in BM. The PB and BM were collected on the same day from 164 blood disease patients, including 118 AML patients. WT1 mRNA expression was determined using the new and former kits and the values obtained were compared. The performance of new kit was shown to be equivalent to that of former kit. As reported in PB, WT1 mRNA expression in BM was found to be a useful marker for monitoring disease status as well as for a diagnosis of early stage relapse in AML patients.

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References

  1. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell. 1990;60:509–20.

    Article  PubMed  CAS  Google Scholar 

  2. Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletion in Wilms tumors of a zinc-finger gene identified by chromosome jumping. Nature. 1990;343:774–8.

    Article  PubMed  CAS  Google Scholar 

  3. Rauscher FJ 3rd. The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor. FASEB J. 1993;7:896–903.

    PubMed  CAS  Google Scholar 

  4. Inoue K, Sugiyama H, Ogawa H, Nakagawa M, Yamagami T, Miwa H, et al. WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood. 1994;84:3071–9.

    PubMed  CAS  Google Scholar 

  5. Oji Y, Ogawa H, Tamaki H, Oka Y, Tsuboi A, Kim EH, et al. Expression of the Wilms’ tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res. 1999;90:194–204.

    Article  PubMed  CAS  Google Scholar 

  6. Sugiyama H. Wilms’ tumor gene WT1: its oncogenic function and clinical application. Int J Hematol. 2001;73:177–87.

    Article  PubMed  CAS  Google Scholar 

  7. Inoue K, Ogawa H, Yamagami T, Soma T, Tani Y, Tatekawa T, et al. Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels. Blood. 1996;88:2267–78.

    PubMed  CAS  Google Scholar 

  8. Miyawaki S, Emi N, Mitani K, Oyashiki K, Kitamura K, Morishita T. Clinical course of the disease and the level of WT1 mRNA in patients with acute myeloid leukemia (AML): joint research by 23 institutions in Japan. Jpn J Clin Hematol. 2005;46(12):1279–87.

    Google Scholar 

  9. Trka J, Kalinová M, Hrusák O, Zuna J, Krejcí O, Madzo J, et al. Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia. 2002;16(7):1381–9.

    Article  PubMed  CAS  Google Scholar 

  10. Cilloni D, Gottardi E, De Micheli D, Serra A, Volpe G, Messa F, et al. 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. 2002;16(10):2115–21.

    Article  PubMed  CAS  Google Scholar 

  11. Tamaki H, Mishima M, Kawakami M, Tsuboi A, Kim EH, Hosen N, et al. Monitoring minimal residual disease in leukemia using real-time quantitative polymerase chain reaction for Wilms tumor gene (WT1). Int J Hematol. 2003;78(4):349–56.

    Article  PubMed  CAS  Google Scholar 

  12. Østergaard M, Olesen LH, Hasle H, Kjeldsen E, Hokland P. WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70 % of acute myeloid leukaemia patients—results from a single-centre study. Br J Haematol. 2004;125:590–600.

    Article  PubMed  Google Scholar 

  13. Weisser M, Kern W, Rauhut S, Schoch C, Hiddemann W, Haferlach T, et al. Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. Leukemia. 2005;19:1416–23.

    Article  PubMed  CAS  Google Scholar 

  14. Kitamura K, Nakano Y, Watamoto K, Koga D, Naoe T. Significance of monitoring WT1 mRNA levels of peripheral blood and bone marrow in acute myeloid leukemia. Jpn J Clin Hematol. 2010;51(12):1748–55.

    Google Scholar 

  15. Cilloni D, Renneville A, Hermitte F, Hills RK, Daly S, Jovanovic JV, et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WTl assay to enhance risk stratification in acute myeloid leukemia: a European leukemia net study. J Clin Oncol. 2009;27(31):5195–201.

    Article  PubMed  CAS  Google Scholar 

  16. Miyawaki S, Hatsumi N, Tamaki T, Naoe T, Ozawa K, Kitamura K, et al. Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia. Leuk Lymphoma. 2010;51(10):1855–61.

    Article  PubMed  CAS  Google Scholar 

  17. Ommen HB, Nyvold CG, Braendstrup K, Andersen BL, Ommen IB, Hasle H, et al. 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. 2008;141(6):782–91.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo Ichinomiya, Aichi, 491-8558, Japan

    Kunio Kitamura & Takahiro Nishiyama

  2. Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan

    Ken Ishiyama & Shuichi Miyawaki

  3. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

    Kanji Miyazaki & Kenshi Suzuki

  4. Department of Hematology and Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Hiroaki Masaie

  5. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    Masaya Okada & Hiroyasu Ogawa

  6. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Kiyotoshi Imai

  7. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Aichi, Japan

    Takahiro Nishiyama, Hitoshi Kiyoi & Tomoki Naoe

  8. Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Yasuhisa Yokoyama & Shigeru Chiba

  9. Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

    Tomoko Hata & Yasushi Miyazaki

  10. Department of Hematology and Rheumatology, Nihon University School of Medicine, Itabashi Hospital, Tokyo, Japan

    Yoshihiro Hatta & Jin Takeuchi

  11. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Yasuhito Nannya & Mineo Kurokawa

  12. Department of Haematology/Oncology, Transfusion and Haemapheresis Center, Kurashiki Central Hospital, Okayama, Japan

    Yasunori Ueda

  13. Diagnostic Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan

    Daisuke Koga

  14. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan

    Haruo Sugiyama

  15. The Japanese Association of Medical Sciences, Tokyo, Japan

    Fumimaro Takaku

  16. Department of Hematology, Kanazawa University Hospital, Ishikawa, Japan

    Ken Ishiyama

  17. National Hospital Organization Nagoya Medical Center, Aichi, Japan

    Tomoki Naoe

  18. Division of Hematology, International University of Health and Welfare Shioya Hospital, Tochigi, Japan

    Jin Takeuchi

Authors
  1. Kunio Kitamura
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  2. Takahiro Nishiyama
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  3. Ken Ishiyama
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  4. Shuichi Miyawaki
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  5. Kanji Miyazaki
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  6. Kenshi Suzuki
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  7. Hiroaki Masaie
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  8. Masaya Okada
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  9. Hiroyasu Ogawa
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  10. Kiyotoshi Imai
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  11. Hitoshi Kiyoi
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  12. Tomoki Naoe
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  13. Yasuhisa Yokoyama
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  14. Shigeru Chiba
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  15. Tomoko Hata
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  16. Yasushi Miyazaki
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  17. Yoshihiro Hatta
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  18. Jin Takeuchi
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  19. Yasuhito Nannya
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  20. Mineo Kurokawa
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  21. Yasunori Ueda
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  22. Daisuke Koga
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  23. Haruo Sugiyama
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  24. Fumimaro Takaku
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Corresponding author

Correspondence to Kunio Kitamura.

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Conflict of interest

This study was funded by Otsuka Pharmaceutical Co., Ltd. K.K. received research funding from Otsuka during the conduct of the study. T. Nishiyama, S.M., K.M., K.S., H.M., M.O., H.O., K. Imai, H.K., Y.Y., S.C., T.H., Y.M., Y.H., J.T., Y. N., M.K. and Y.U. received research funding from Otsuka during the conduct of the study. K. Ishiyama and T. Naoe received research funding and personal fees from Otsuka during the conduct of the study. H.S. received personal fees from Otsuka during the conduct of the study. D.K. is employee of Otsuka. F.T. declares no conflict of interest.

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Kitamura, K., Nishiyama, T., Ishiyama, K. et al. Clinical usefulness of WT1 mRNA expression in bone marrow detected by a new WT1 mRNA assay kit for monitoring acute myeloid leukemia: a comparison with expression of WT1 mRNA in peripheral blood. Int J Hematol 103, 53–62 (2016). https://doi.org/10.1007/s12185-015-1882-1

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  • DOI: https://doi.org/10.1007/s12185-015-1882-1

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