AUTHOR=Wang Yin , Weng Wen-Jun , Zhou Dun-Hua , Fang Jian-Pei , Mishra Srishti , Chai Li , Xu Lu-Hong 

TITLE=Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.632094

DOI=10.3389/fonc.2021.632094

ISSN=2234-943X

ABSTRACT=<p>The prognostic impact of <italic>Wilms tumor 1</italic> (<italic>WT1</italic>) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of <italic>WT1</italic> 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 <italic>WT1</italic> mutations in this cohort. Our results showed that 6.7% of total patients harbored <italic>WT1</italic> mutations. These <italic>WT1</italic> mutations were closely associated with normal cytogenetics (<italic>P</italic>&lt;0.001), FMS-like tyrosine kinase 3/internal tandem duplication (<italic>FLT3</italic>/ITD) mutations (<italic>P</italic>&lt;0.001), and low complete remission induction rates (<italic>P</italic>&lt;0.01). Compared to the patients without <italic>WT1</italic> mutations, patients with <italic>WT1</italic> mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, <italic>P</italic>&lt;0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, <italic>P</italic>&lt;0.001). Moreover, patients with both <italic>WT1</italic> and <italic>FLT3</italic>/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of <italic>WT1</italic>-mutated patients. Multivariate analysis demonstrated that <italic>WT1</italic> mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, <italic>P</italic> = 0.001) and overall survival (hazard ratio 1.709, <italic>P</italic> = 0.020). In conclusion, our findings have demonstrated that <italic>WT1</italic> mutations are independent poor prognostic factors in pediatric AML.</p>