Single Nucleotide Polymorphism in the Mutational Hotspot of WT1 Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia.
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Single Nucleotide Polymorphism in the Mutational Hotspot of WT1 Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia. / Damm, Frederik; Heuser, Michael; Morgan, Michael; Yun, Haiyang; Großhennig, Anika; Göhring, Gudrun; Schlegelberger, Brigitte; Döhner, Konstanze; Ottmann, Oliver; Lübbert, Michael; Heit, Wolfgang; Kanz, Lothar; Schlimok, Günter; Raghavachar, Aruna; Fiedler, Walter; Kirchner, Hartmut; Döhner, Hartmut; Heil, Gerhard; Ganser, Arnold; Krauter, Jürgen.
In: J CLIN ONCOL, 2009.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Single Nucleotide Polymorphism in the Mutational Hotspot of WT1 Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia.
AU - Damm, Frederik
AU - Heuser, Michael
AU - Morgan, Michael
AU - Yun, Haiyang
AU - Großhennig, Anika
AU - Göhring, Gudrun
AU - Schlegelberger, Brigitte
AU - Döhner, Konstanze
AU - Ottmann, Oliver
AU - Lübbert, Michael
AU - Heit, Wolfgang
AU - Kanz, Lothar
AU - Schlimok, Günter
AU - Raghavachar, Aruna
AU - Fiedler, Walter
AU - Kirchner, Hartmut
AU - Döhner, Hartmut
AU - Heil, Gerhard
AU - Ganser, Arnold
AU - Krauter, Jürgen
PY - 2009
Y1 - 2009
N2 - PURPOSE: We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers. PATIENTS AND METHODS: WT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified. RESULTS: The minor allele of SNP rs16754 (WT1(AG/GG)) was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of healthy volunteers. Patient characteristics, frequencies of mutations, or WT1 expression levels were similarly distributed between patients homozygous for the major allele compared with patients heterozygous or homozygous for the minor allele. SNP rs16754 status was an independent predictor of relapse-free survival (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis. The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3-ITD low-risk patients. Favorable prognosis could not be identified by any other known low-risk marker in half the patients with at least one minor allele (13% of all patients). No difference for complete remission rate, RFS, or OS was found between patients with or without acquired WT1 mutations. CONCLUSION: WT1 SNP rs16754 may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.
AB - PURPOSE: We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers. PATIENTS AND METHODS: WT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified. RESULTS: The minor allele of SNP rs16754 (WT1(AG/GG)) was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of healthy volunteers. Patient characteristics, frequencies of mutations, or WT1 expression levels were similarly distributed between patients homozygous for the major allele compared with patients heterozygous or homozygous for the minor allele. SNP rs16754 status was an independent predictor of relapse-free survival (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis. The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3-ITD low-risk patients. Favorable prognosis could not be identified by any other known low-risk marker in half the patients with at least one minor allele (13% of all patients). No difference for complete remission rate, RFS, or OS was found between patients with or without acquired WT1 mutations. CONCLUSION: WT1 SNP rs16754 may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.
M3 - SCORING: Zeitschriftenaufsatz
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
ER -
