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Acute Lymphoblastic Leukemia

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring

Leukemia volume 20, pages 254–263 (2006)Cite this article

Abstract

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70–90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (⩾10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) ⩾50 × 109/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

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Acknowledgements

We thank Katerina Muzikova from the laboratories of Department of Pediatric Hematology and Oncology, Prague, for the help with processing of samples, Tony Fitzgerald from Haughton Institute, St James's Hospital, Dublin and Marek Omelka from Deptartment of probability and mathematical statistics, Faculty of mathematics and physics of Charles University, Prague, for the help with statistical evaluation of the data. The collaboration of the Czech Pediatric Hematology Working Group centers is highly appreciated. This work has been supported by the HEA PRTLI, Children's Leukemia Research Project, Children's Medical and Research Foundation OLHSC, IGA (Czech Ministry of Health) 7439 and MSM (Czech Ministry of Education) 0021620813.

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Authors and Affiliations

  1. Department of Hematology, Durkan Leukemia Research Laboratories, Institute of Molecular Medicine, Trinity College and St James's Hospital, Dublin, Ireland

    L Boublikova, J Ryan, F Quinn, P Browne, S R McCann & M Lawler

  2. Department of Pediatric Hematology and Oncology, 2nd Medical School, Charles' University and University Hospital in Prague – Motol, Czech Republic

    M Kalinova, J Stary & J Trka

  3. Department of Hematology, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland

    A O'Marcaigh & O Smith

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  1. L Boublikova
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Boublikova, L., Kalinova, M., Ryan, J. et al. Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring. Leukemia 20, 254–263 (2006). https://doi.org/10.1038/sj.leu.2404047

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