Abstract
The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P<0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.
Highlights
Acute myeloid leukemia (AML) is a type of blood cancer that originates in the bone marrow from immature white blood cells known as myeloblasts
We found that Wilms tumor 1 (WT1) mutations are independent poor prognostic factors in pediatric AML in terms of 5-year event-free survival (EFS) and overall survival (OS)
We evaluated the associations between WT1 mutations and cytogenetic and molecular alterations
Summary
Acute myeloid leukemia (AML) is a type of blood cancer that originates in the bone marrow from immature white blood cells known as myeloblasts. About 20% of all children with leukemia have AML [1, 2]. WT1 Mutations in Pediatric AML and guiding post-induction treatment [3]. The Wilms tumor 1 (WT1) gene, located on chromosome 11p13, encodes a zincfinger protein that exists in multiple isoforms. It has been implicated in the regulation of cell survival, proliferation and differentiation, and may function both as a tumor suppressor and an oncogene [4, 5]. Various mutations across WT1 gene have been reported in solid tumors and AML [6, 7]. The prognostic impact of WT1 mutations remains controversial for patients with AML [8]
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