scholarly journals Wilms' tumor 1 single-nucleotide polymorphism rs16754 does not predict clinical outcome in adult acute myeloid leukemia

Leukemia ◽  
2011 ◽  
Vol 25 (12) ◽  
pp. 1918-1921 ◽  
Author(s):  
A Renneville ◽  
N Boissel ◽  
N Helevaut ◽  
O Nibourel ◽  
C Terré ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Wilms Tumor 1 ◽  
Acute Myeloid

Mutation and Single-Nucleotide Polymorphism (rs16754) in Wilms Tumor-1 Gene Are Independent Prognostic Factors in Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 995-995 ◽  
Author(s):  
Wanlong Ma ◽  
Hagop Kantarjian ◽  
XI Zhang ◽  
Xiuqiang Wang ◽  
Zhong Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Wilms Tumor 1 ◽  
Wt1 Mutation ◽  
Acute Myeloid

Abstract Abstract 995 Poster Board I-17 Several reports have suggested that mutations in the Wilms tumor 1 gene (WT1) represent an adverse prognostic factor in acute myeloid leukemia (AML). Here we examined the associations of WT1 mutations in exons 7 and 9 and the silent R301 single-nucleotide polymorphism (SNP) in exon 7 (A903G; NCBI dbSNP reference ID: rs16754) with outcome in AML patients treated at a single institution. Peripheral blood plasma and bone marrow samples from 174 newly diagnosed AML patients were tested for WT1 mutations in exons 7 and 9 by sequencing and fragment-length analysis for the detection of small deletions/insertions. Sequencing provided information on the specific genotype of the rs16754 SNP. The findings were correlated with outcome and other laboratory findings. WT1 mutation was detected in 7 of 50 (14%) AML patients <50 years of age and in 5 of 124 (4%) patients >50. The silent R301 SNP was detected at frequencies of 4% for GG, 26% for GA, and 70% for AA genotypes, but there was no difference with age. A similar SNP genotype distribution was detected in normal control subjects. WT1 mutations were associated with higher white cell count (P=0.01) and higher percentage of blasts in bone marrow (P=0.03) and peripheral blood (P=0.009). In addition, WT1 mutation was significantly associated with FLT3 mutation (P=0.002) but not NPM1 mutation (P=0.8). WT1 mutation was also significantly associated with shorter survival (P=0.025), event-free survival (P=0.002), and complete remission duration (P=0.002) in patients <50 years of age, but not in older patients. The association with shorter survival persisted when only patients with intermediate cytogenetics were considered (P=0.03). There was no correlation between WT1 mutation and response to therapy. The most striking correlation was between the presence of the GG genotype at R301 and longer survival, irrespective of age (see survival chart below). There was no difference in survival between the AA and GA groups. To the best of our knowledge, this is the first report describing correlation between survival duration and an SNP in the WT1 gene. While we confirm that the presence of WT1 mutation is associated with poor outcome in young AML patients, our data suggest that there is no clinical value in testing patients older than 50 for WT1 mutation, but that there may be value in testing adult patients of all age groups for the SNP polymorphism at R301 Disclosures: No relevant conflicts of interest to declare.

No Prognostic Impact of the WT1 Gene Single Nucleotide Polymorphism rs16754 in Pediatric Acute Myeloid Leukemia

2010 ◽  
Vol 28 (28) ◽  
pp. e523-e526 ◽  
Author(s):  
Iris H.I.M. Hollink ◽  
Marry M. van den Heuvel-Eibrink ◽  
Martin Zimmermann ◽  
Brian V. Balgobind ◽  
Susan T.C.J.M. Arentsen-Peters ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Wt1 Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pediatric Acute Myeloid Leukemia ◽  
Gene Single Nucleotide Polymorphism ◽  
Acute Myeloid

scholarly journals Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3932-3941 ◽  
Author(s):  
Anna M. Jankowska ◽  
Hideki Makishima ◽  
Ramon V. Tiu ◽  
Hadrian Szpurka ◽  
Yun Huang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Molecular Heterogeneity ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Mutant Genotype ◽  
Myelomonocytic Leukemia ◽  
Acute Myeloid

Abstract Chronic myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm, is characterized by monocytic proliferation, dysplasia, and progression to acute myeloid leukemia. CMML has been associated with somatic mutations in diverse recently identified genes. We analyzed 72 well-characterized patients with CMML (N = 52) and CMML-derived acute myeloid leukemia (N = 20) for recurrent chromosomal abnormalities with the use of routine cytogenetics and single nucleotide polymorphism arrays along with comprehensive mutational screening. Cytogenetic aberrations were present in 46% of cases, whereas single nucleotide polymorphism array increased the diagnostic yield to 60%. At least 1 mutation was found in 86% of all cases; novel UTX, DNMT3A, and EZH2 mutations were found in 8%, 10%, and 5.5% of patients, respectively. TET2 mutations were present in 49%, ASXL1 in 43%, CBL in 14%, IDH1/2 in 4%, KRAS in 7%, NRAS in 4%, and JAK2 V617F in 1% of patients. Various mutant genotype combinations were observed, indicating molecular heterogeneity in CMML. Our results suggest that molecular defects affecting distinct pathways can lead to similar clinical phenotypes.

Single Nucleotide Polymorphism in the Mutational Hotspot of WT1 Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia

2010 ◽  
Vol 28 (4) ◽  
pp. 578-585 ◽  
Author(s):  
Frederik Damm ◽  
Michael Heuser ◽  
Michael Morgan ◽  
Haiyang Yun ◽  
Anika Großhennig ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Healthy Volunteers ◽  
Myeloid Leukemia ◽  
Minor Allele ◽  
Risk Marker ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Risk Patients ◽  
Acute Myeloid

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 (WT1AG/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.

scholarly journals A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia

2007 ◽  
Vol 117 (9) ◽  
pp. 2611-2620 ◽  
Author(s):  
Ulrich Steidl ◽  
Christian Steidl ◽  
Alexander Ebralidze ◽  
Björn Chapuy ◽  
Hye-Jung Han ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Long Range ◽  
Myeloid Leukemia ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Acute Myeloid
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