Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia.

Hollink IH; van den Heuvel-Eibrink MM; Zimmermann M; Balgobind BV; Arentsen-Peters ST; Alders M; Willasch A; Kaspers GJ; Trka J; Baruchel A; de Graaf SS; Creutzig U; Pieters R; Reinhardt D; Zwaan CM

doi:10.1182/blood-2008-09-177949

Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia.

Hollink IH ¹,

van den Heuvel-Eibrink MM ,

Trka J ,

Affiliations

1. Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Authors
Hollink IH¹
(1 author)

ORCIDs linked to this article

Blood, 26 Jan 2009, 113(23):5951-5960
https://doi.org/10.1182/blood-2008-09-177949 PMID: 19171881

A comment on this article appears in "Adding WT1 to childhood AML alphabet soup." Blood. 2009 Jun 4;113(23):5696-7.

Abstract

Wilms tumor 1 (WT1) mutations have recently been identified in approximately 10% of adult acute myeloid leukemia (AML) with normal cytogenetics (CN-AML) and are associated with poor outcome. Using array-based comparative genome hybridization in pediatric CN-AML samples, we detected a WT1 deletion in one sample. The other WT1 allele was mutated. This prompted us to further investigate the role of WT1 aberrations in childhood AML. Mutations were found in 35 of 298 (12%) diagnostic pediatric AML samples. In 19 of 35 (54%) samples, more than one WT1 aberration was found: 15 samples had 2 different mutations, 2 had a homozygous mutation, and 2 had a mutation plus a WT1 deletion. WT1 mutations clustered significantly in the CN-AML subgroup (22%; P < .001) and were associated with FLT3/ITD (43 vs 17%; P < .001). WT1 mutations conferred an independent poor prognostic significance (WT1 mutated vs wild-type patients: 5-year probability of overall survival [pOS] 35% vs 66%, P = .002; probability of event-free survival 22% vs 46%, P < .001; and cumulative incidence of relapse or regression 70% vs 44%, P < .001). Patients with both a WT1 mutation and a FLT3/ITD had a dismal prognosis (5-year pOS 21%). WT1 mutations occur at a significant rate in childhood AML and are a novel independent poor prognostic marker.

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Catalogue Of Somatic Mutations In Cancer

https://cancer.sanger.ac.uk/cosmic/study/overview?pmid=19171881

Proteins in UniProt (Showing 5 of 11)

C2H2-type domain-containing protein(UniProt - A0FJ57)
C2H2-type domain-containing protein(UniProt - A0FJ58)
Wilm's tumour protein N-terminal domain-containing protein(UniProt - A8MN20)
C2H2-type domain-containing protein(UniProt - Q6LBI3)
Wilm's tumour protein N-terminal domain-containing protein(UniProt - Q6PI38)

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