Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.
Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring.



Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse.



We found that overexpression of the WT1 gene (WT1highstatus), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1highstatus was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of < 2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3-ITD-/NPM1-double negative) with WT1highstatus is almost the same as the tumor behavior of the adverse risk group.



WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols.
Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Irena
I
Marjanovic
Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Teodora
T
Karan-Djurasevic
Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Milena
M
Ugrin
Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
Marijana
M
Virijevic
Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia.
Ana
A
Vidovic
Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia.
Dragica
D
Tomin
Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia.
Nada
N
Suvajdzic Vukovic
Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Sonja
S
Pavlovic
Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: natasa.tosic@imgge.bg.ac.rs.
Natasa
N
Tosic
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D016162:Genes, Wilms Tumor; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000090243:Nucleophosmin; D011379:Prognosis; D059467:Transcriptome; D025721:WT1 Proteins / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; D000090243:Nucleophosmin
AML with normal karyotype; Minimal residual disease; Prognosis; Real-time PCR; WT1 expression