Clinical significance of quantitation of WT1 gene expression for minimal residual disease monitoring of acute myelogenous leukemia

Abstract

BACKGROUND: Following induction chemotherapy for AML, a sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse. This study was designed to verify if quantitative assessment of the Wilms' tumor (WT1) gene by real time polymerase chain reaction (RQ-PCR) can be used as a marker for MRD detection during the monitoring of AML. METHODS: WT1 gene expression was quantified by RQ-PCR in 31 patients with AML at diagnosis (27 patients) and during follow-up (29 patients) relative to ABL control gene. In four patients, the WT1 gene expression was analyzed in comparison to a second PCR marker, PML-RARA fusion transcript. Prognostic significance of WT1 gene expression was analyzed at diagnosis and at the primary CR evaluation. Longitudinal WT1 gene analysis was performed in 17 AML patients. RESULTS: At diagnosis, WT1 gene expression exceeded the control level in all of the patients. Higher levels of WT1 gene expression were not associated with shorter event free survival or overall survival at diagnosis. Higher levels of WT1 gene expression were associated with shorter event free survival after induction chemotherapy. Relapse was observed in eight of 17 patients analysed longitudinally, and an increase of WT1 gene expression preceded morphologic relapse in four patients with the fusion transcript negative. Concomitant monitoring of PML-RARA fusion transcript reveals the lack of a significant correlation withWT1 gene expression. CONCLUSIONS: Quantitation of WT1 gene expression could be used for MRD monitoring of AML and for the early detection of relapse, especially in patients lacking specific molecular markers.