The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients

Abstract

Introduction: Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring.

Methods: Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring.

Results: Increased WT1 expression was found in 34% of patients. WT1^high status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring.

Conclusion: Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.

Keywords: WT1 gene expression; acute promyelocytic leukemia; minimal residual disease; prognosis.