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Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia†‡

A Study From the Acute Leukemia French Association

  1. Aline Renneville MD1,2,3,§,
  2. Nicolas Boissel MD, PhD4,5,§,
  3. Virginie Zurawski MD1,2,3,
  4. Laura Llopis MD1,2,3,
  5. Valéria Biggio PhD1,2,3,
  6. Olivier Nibourel MD1,2,3,
  7. Nathalie Philippe PhD1,2,3,
  8. Xavier Thomas MD6,
  9. Hervé Dombret MD4,5,
  10. Claude Preudhomme MD, PhD1,2,3,¶,*

Article first published online: 17 JUN 2009

DOI: 10.1002/cncr.24442

Issue

Cancer

Cancer

Volume 115, Issue 16, pages 3719–3727, 15 August 2009

Additional Information

How to Cite

Renneville, A., Boissel, N., Zurawski, V., Llopis, L., Biggio, V., Nibourel, O., Philippe, N., Thomas, X., Dombret, H. and Preudhomme, C. (2009), Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia. Cancer, 115: 3719–3727. doi: 10.1002/cncr.24442

Author Information

  1. 1

    Department of Hematology, Biology and Pathology Center, University of Lille Medical School, Lille, France

  2. 2

    Cancer Research Institute, J. P. Aubert Center, Inserm U-837, Team 3, Lille, France

  3. 3

    Onco-Hematology Axis, Northwest Canceropole, Lille, France

  4. 4

    EA 3518, University of Paris, Paris, France

  5. 5

    Department of Adult Hematology, St. Louis Hospital, Paris, France

  6. 6

    Department of Hematology, Edouard Herriot Hospital, Lyon, France

  1. §

    The two first authors contributed equally to this article.

  2. Fax: (011) 333-20-44-6989

*Department of Hematology, Biology and Pathology Center, Professor Leclercq Boulevard, 59037 Lille Cedex, France

  1. †

    We thank all patients and members of the Acute Leukemia French Association for their participation.

  2. ‡

    The following additional members of the Acute Leukemia French Association (ALFA) contributed to this work: Sandrine Hayette, MD (Department of Cytogenetics and Molecular Biology, Edouard Herriot Hospital, Lyon, France) Stéphane de Botton, MD, PhD (Gustave Roussy Institute, Villejuif, France) Jean-Michel Cayuela, MD, PhD (Department of Hematology, St. Louis Hospital, Paris, France) Dominique Bories, MD (Department of Hematology, Henri Mondor Hospital, Créteil, France); Xavier Troussard, MD (Department of Hematology, Caen Hospital, Caen, France); Christine Terré, MD (Department of Cytogenetics, André Mignot Hospital, Versailles, France); and Sylvie Castaigne, MD (Department of Hematology and Oncology, André Mignot Hospital, Versailles, France).

Publication History

  1. Issue published online: 3 AUG 2009
  2. Article first published online: 17 JUN 2009
  3. Manuscript Accepted: 22 JAN 2009
  4. Manuscript Revised: 19 JAN 2009
  5. Manuscript Received: 4 SEP 2008

Funded by

  • Fondation de France (Leukemia Committee)
  • North-West Canceropole (Onco-Hematology Axis)

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Keywords:

  • acute myeloid leukemia;
  • adult;
  • Wilms tumor 1 mutations;
  • frequency;
  • prognosis

In the current study, the authors retrospectively screened Wilms tumor 1 (WT1) exon 7 and 9 mutations in a cohort of 268 young adults with acute myeloid leukemia (AML) who were treated on the Acute Leukemia French Association 9802 trial. Patients with WT1 mutations had a shorter overall survival (P = .01) and a higher risk of recurrence (P = .0008) than patients with the wild–type WT1.

Abstract

BACKGROUND:

Wilms tumor 1 (WT1) is a transcription factor that is overexpressed in most acute myeloid leukemias (AMLs). Recently, 2 groups reported that WT1 mutations occur in approximately 10% of normal karyotype AMLs and are an independent predictor of poor outcome in this subgroup of patients with AML.

METHODS:

The authors studied a cohort of 268 young adults (ages 15-50 years) with AML who were treated on the Acute Leukemia French Association 9802 trial. WT1 exon 7 and 9 mutations were screened retrospectively by polymerase chain reaction and direct sequencing. The patients also were assessed for the presence of the fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD), FLT3-D835/I836, nucleophosmin 1 (NPM1), and CCAAT/enhancer binding protein α (CEBPA) mutations.

RESULTS:

WT1 mutations were identified in 14 patients (5%) and were associated with a younger age (P = .02) and an FLT3-ITD (P = .03). No mutation was detected in patients who had favorable cytogenetics. Patients who had WT1 mutations had a shorter overall survival at 4 years (22% vs 56%; P = .01) and a higher risk of recurrence at 4 years (82% vs 46%; P = .0008) compared with patients who had wild-type WT1. Within the subgroup of patients who had normal karyotype AML (n = 106), WT1 mutation was identified as an independent adverse prognostic factor for the risk of recurrence.

CONCLUSIONS:

The current results indicted that WT1 mutations represent an adverse prognostic factor in young adults with AML. Prospective trials should confirm the clinical relevance of WT1 mutations in relation to other prognostic factors in patients with AML. Cancer 2009. © 2009 American Cancer Society.

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