Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group.
To evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Group protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1(mut)) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1(mut)/FLT3-ITD(pos) had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1(mut)/FLT3-ITD(neg). In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1(mut)/FLT3-ITD(pos).
Gaidzik
Verena Ingeborg
VI
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Schlenk
Richard Friedrich
RF
Moschny
Simone
S
Becker
Annegret
A
Bullinger
Lars
L
Corbacioglu
Andrea
A
Krauter
Jürgen
J
Schlegelberger
Brigitte
B
Ganser
Arnold
A
Döhner
Hartmut
H
Döhner
Konstanze
K
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001317:Austria; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D005858:Germany; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D020080:Tandem Repeat Sequences / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D014408:Biomarkers, Tumor; D025721:WT1 Proteins; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3