Irena Marjanovic1, Teodora Karan-Djurasevic1, Milena Ugrin1, Marijana Virijevic2, Ana Vidovic3, Dragica Tomin3, Nada Suvajdzic Vukovic3, Sonja Pavlovic1, Natasa Tosic4. 1. Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. 2. Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia. 3. Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia. 4. Laboratory for Molecular Biomedicine, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: natasa.tosic@imgge.bg.ac.rs.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: We found that overexpression of the WT1 gene (WT1high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1high status 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 WT1high status is almost the same as the tumor behavior of the adverse risk group. CONCLUSION: 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.
BACKGROUND:Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AMLpatients 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. PATIENTS AND METHODS: 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-NKpatients and from 34 of these patients during follow-up or disease relapse. RESULTS: We found that overexpression of the WT1 gene (WT1high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1high status 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 WT1high status is almost the same as the tumor behavior of the adverse risk group. CONCLUSION: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-NKpatients could lead to more adapted, personalized treatment protocols.