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Wilms Tumor 1 (WT1) is overexpressed in approximately 85% of Acute Myeloid Leukemia (AML) patients and it is associated with poor outcomes in this group of patients. There is a paucity of studies that have investigated WT1 as a marker for risk stratification especially in Normal Karyotype AML (NK-AML).
In an article published in Clinical Lymphoma, Myeloma & Leukemia, Irena Marjanovic and colleagues from the University of Belgrade, Serbia, aimed to investigate the use of WT1 as a biomarker and also evaluate its potential as a Measurable Residual Disease (MRD) marker in patients with NK-AML.
In total, 104 AML-NK patient bone marrow samples at diagnosis and disease relapse were analyzed for WT1 gene expression. At diagnosis, 98 patients had detectable WT1 gene expression.
In summation, “WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring”.
The authors concluded by suggesting that WT1 gene expression level should be used as an additional marker for “more precise risk stratification of AML-NK patients” as this could lead to a more “refined treatment protocol in which WT1 targeted therapy can be applied”.
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 (WT1 high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1 high 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 WT1 high status 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.
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