The prognostic effect of high diagnostic WT1 gene expression in pediatric AML depends on WT1 SNP rs16754 status: Report from the Children's Oncology Group. Issue 1 (16th August 2013)

• Record Type: Journal Article
• Authors: Ho, Phoenix A.; Alonzo, Todd A.; Gerbing, Robert B.; Kuhn, Julia; Pollard, Jessica A.; Hirsch, Betsy; Raimondi, Susana C.; Gamis, Alan S.; Meshinchi, Soheil
• Is Part Of: Pediatric blood & cancer. Volume 61:Issue 1(2014:Jan.)
• Page Start: 81
• Page End: 88
• Publication Date: 2013-08-16
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24700
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pbc24700-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>WT1</italic> is aberrantly over‐expressed in most cases of AML. We recently demonstrated that <italic>WT1 SNP</italic> rs16754 correlates with favorable outcome and high diagnostic <italic>WT1</italic> expression in childhood AML. We examined the clinical correlates of diagnostic <italic>WT1</italic> expression within a contemporary COG trial and determined whether its prognostic impact differs between SNP+ and SNP− patients.</p> </sec> <sec id="pbc24700-sec-0002" sec-type="section"> <title>Procedure</title> <p> <italic>WT1</italic> mRNA expression was measured via qRT‐PCR in diagnostic specimens obtained from 225 patients enrolled on COG‐AAML03P1. Direct sequencing of <italic>WT1</italic> exon 7 was performed to determine SNP rs16754 genotype. <italic>WT1</italic> expression was correlated with disease characteristics, SNP status, and outcome.</p> </sec> <sec id="pbc24700-sec-0003" sec-type="section"> <title>Results</title> <p>Patients were categorized into four groups (quartiles: Q1 through Q4) based on diagnostic <italic>WT1</italic> expression for analysis. <italic>FLT3/ITD</italic> (<italic>P</italic> = 0.017) and <italic>WT1</italic> mutations (<italic>P</italic> < 0.001) both occurred more frequently in patients with the highest <italic>WT1</italic> expression. SNP rs16754 frequency did not vary significantly among the quartiles. When all patients were considered, survival outcomes were similar between quartiles. However, when only SNP− patients (n = 150) were analyzed, those with highest <italic>WT1</italic> expression (Q4) had the poorest OS (51% vs. 72% for Q1–Q3, <italic>P</italic> = 0.006) and EFS (35% vs. 54% for Q1–Q3, <italic>P</italic> = 0.031). Among SNP+ patients (n = 75), survival did not vary significantly between <italic>WT1</italic> expression quartiles.</p> </sec> <sec id="pbc24700-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Although <italic>WT1</italic> expression was not prognostic when all patients were considered together, stratifying patients by SNP rs16754 genotype revealed significant differences in outcome. In SNP− patients, high <italic>WT1</italic> expression predicted decreased survival in univariate, but not multivariate, analysis, due to a preponderance of high‐risk cyto/molecular abnormalities in the highest expression quartile. Pediatr Blood Cancer 2014;61:81–88. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>