Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 3/2015

01.03.2015 | Original Article – Clinical Oncology

Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases

verfasst von: Caroline Woehlecke, Susan Wittig, Clemens Arndt, Bernd Gruhn

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Malignant hematological diseases represent the most common pediatric cancer. As they cannot always be cured by chemotherapy alone, leukemia and myelodysplastic syndrome (MDS) are frequent medical indications for hematopoietic stem cell transplantation, yet even this treatment is not capable of preventing relapse for certain. Therefore, molecular markers are used to monitor minimal residual disease (MRD) to be enabled to react early to an impeding relapse. As specific markers are not always available, Wilms’ tumor gene 1 (WT1) has been suggested as a universal marker, but has not yet been established clinically.

Methods

We determined the level of WT1 gene expression in 130 children, adolescents and young adults with malignant hematological diseases prior to transplantation and evaluated its impact on patients’ outcome. A real-time quantitative RT-PCR was used for this purpose.

Results

The relationship between a high level of WT1 and the cumulative incidence of relapse, event-free survival and overall survival proved to be highly significant in univariate and multivariate analyses. Forty-eight percent of all patients with high WT1 levels suffered from a relapse, whereas only eight percent showing normal WT1 levels before transplantation relapsed. The most convincing result was found for acute myeloid leukemia (AML) and MDS.

Conclusion

We conclude that WT1 expression prior to transplantation qualifies as an independent prognostic factor and should be further evaluated for MRD monitoring. It might especially be useful for patients with AML or MDS missing specific markers.
Literatur
Zurück zum Zitat Boublikova L et al (2006) 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. doi:10.1038/sj.leu.2404047 CrossRefPubMed Boublikova L et al (2006) 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. doi:10.​1038/​sj.​leu.​2404047 CrossRefPubMed
Zurück zum Zitat Call KM et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520CrossRefPubMed Call KM et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520CrossRefPubMed
Zurück zum Zitat Cazzaniga G, dA E, Corral L, Biondi A (2003) Results of minimal residual disease (MRD) evaluation and MRD-based treatment stratification in childhood ALL. Best pract res Clin haematol 15:623–638CrossRef Cazzaniga G, dA E, Corral L, Biondi A (2003) Results of minimal residual disease (MRD) evaluation and MRD-based treatment stratification in childhood ALL. Best pract res Clin haematol 15:623–638CrossRef
Zurück zum Zitat Cilloni D, Saglio G (2004) WT1 as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Haematol 112:79–84. doi:10.1159/000077562 CrossRefPubMed Cilloni D, Saglio G (2004) WT1 as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Haematol 112:79–84. doi:10.​1159/​000077562 CrossRefPubMed
Zurück zum Zitat Cilloni D et al (2003) Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes. J clin oncol: Off J American Soc Clin Oncol 21:1988–1995. doi:10.1200/JCO.2003.10.503 CrossRef Cilloni D et al (2003) Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes. J clin oncol: Off J American Soc Clin Oncol 21:1988–1995. doi:10.​1200/​JCO.​2003.​10.​503 CrossRef
Zurück zum Zitat Gaiger A et al (1999) Wilms’ tumour gene (wt1) expression at diagnosis has no prognostic relevance in childhood acute lymphoblastic leukaemia treated by an intensive chemotherapy protocol. Eur J Haematol 63:86–93CrossRefPubMed Gaiger A et al (1999) Wilms’ tumour gene (wt1) expression at diagnosis has no prognostic relevance in childhood acute lymphoblastic leukaemia treated by an intensive chemotherapy protocol. Eur J Haematol 63:86–93CrossRefPubMed
Zurück zum Zitat Hosen N et al (2002) Very low frequencies of human normal CD34 + haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol 116:409–420CrossRefPubMed Hosen N et al (2002) Very low frequencies of human normal CD34 + haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol 116:409–420CrossRefPubMed
Zurück zum Zitat Inoue K, Sugiyama H, Ogawa H, Nakagawa M, Yamagami T, Miwa 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(9):3071–3079PubMed Inoue K, Sugiyama H, Ogawa H, Nakagawa M, Yamagami T, Miwa 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(9):3071–3079PubMed
Zurück zum Zitat Kwon M et al (2012) Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplantation 18:1235–1242. doi:10.1016/j.bbmt.2012.01.012 CrossRef Kwon M et al (2012) Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplantation 18:1235–1242. doi:10.​1016/​j.​bbmt.​2012.​01.​012 CrossRef
Zurück zum Zitat Lange T et al (2011) Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. Leukemia 25:498–505. doi:10.1038/leu.2010.283 CrossRefPubMed Lange T et al (2011) Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. Leukemia 25:498–505. doi:10.​1038/​leu.​2010.​283 CrossRefPubMed
Zurück zum Zitat Ogawa H et al (2003) The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia. Blood 101:1698–1704. doi:10.1182/blood-2002-06-1831 CrossRefPubMed Ogawa H et al (2003) The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia. Blood 101:1698–1704. doi:10.​1182/​blood-2002-06-1831 CrossRefPubMed
Zurück zum Zitat Sugiyama H (2001) Wilms’ tumor gene WT1: its oncogenic function and clinical application. Int J Hematol 73:177–187CrossRefPubMed Sugiyama H (2001) Wilms’ tumor gene WT1: its oncogenic function and clinical application. Int J Hematol 73:177–187CrossRefPubMed
Zurück zum Zitat Tamaki H et al (1999) The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia 13:393–399CrossRefPubMed Tamaki H et al (1999) The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia 13:393–399CrossRefPubMed
Zurück zum Zitat Trka J et al (2002) 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 16:1381–1389. doi:10.1038/sj.leu.2402512 CrossRefPubMed Trka J et al (2002) 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 16:1381–1389. doi:10.​1038/​sj.​leu.​2402512 CrossRefPubMed
Zurück zum Zitat Valkova V et al (2013) Minimal residual disease detectable by quantitative assessment of WT1 gene before allogeneic stem cell transplantation in patients in first remission of acute myeloid leukemia has an impact on their future prognosis. Clin Transplant 27:E21–29. doi:10.1111/ctr.12046 CrossRefPubMed Valkova V et al (2013) Minimal residual disease detectable by quantitative assessment of WT1 gene before allogeneic stem cell transplantation in patients in first remission of acute myeloid leukemia has an impact on their future prognosis. Clin Transplant 27:E21–29. doi:10.​1111/​ctr.​12046 CrossRefPubMed
Zurück zum Zitat Weisser M, Kern W, Rauhut S, Schoch C, Hiddemann W, Haferlach T, Schnittger S (2005) Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. Leukemia 19:1416–1423. doi:10.1038/sj.leu.2403809 CrossRefPubMed Weisser M, Kern W, Rauhut S, Schoch C, Hiddemann W, Haferlach T, Schnittger S (2005) Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. Leukemia 19:1416–1423. doi:10.​1038/​sj.​leu.​2403809 CrossRefPubMed
Metadaten
Titel
Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases
verfasst von
Caroline Woehlecke
Susan Wittig
Clemens Arndt
Bernd Gruhn
Publikationsdatum
01.03.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1832-y

Weitere Artikel der Ausgabe 3/2015

Journal of Cancer Research and Clinical Oncology 3/2015 Zur Ausgabe

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Medizinstudium Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

06.05.2024 Kolonkarzinom Nachrichten

Menschen mit linksseitigem Kolonkarzinom leben im Mittel zweieinhalb Jahre länger als solche mit rechtsseitigem Tumor. Auch aktuell ist das Sterberisiko bei linksseitigen Tumoren US-Daten zufolge etwa um 11% geringer als bei rechtsseitigen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.