Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia

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Abstract
In search for general PCR targets for minimal residual disease (MRD) studies in acute myeloid leukemia (AML), Wilms' tumor gene 1 (WT1) expression was assessed by real-time RT-PCR relative to the control gene ABL in 569 archived samples of AML patients (pts). Pts were analyzed at diagnosis (n=116) and during follow-up (n=105, median 4 times, range 2–17). Median follow-up time was 258 days (range 16–1578 days). In 66 pts, the WT1 expression was analyzed in comparison to a second PCR marker or to multiparameter flow cytometry. Quantitative WT1 levels correlated to the clinical course or a second marker in 83–96% of the cases. Prognostic significance of WT1 levels was analyzed at diagnosis and three intervals: (1) days 16–60, (2) days 61–120, and (3) days 121–180 after start of chemotherapy. Higher levels of WT1 expression were associated with shorter overall survival (OS) and event-free survival (EFS) within intervals 2 and 3 but not at diagnosis or interval 1. In addition, within these intervals, WT1/ABL levels 0.4% were associated with improved OS and EFS. An increase of WT1 levels was detected in 16/44 cases, which subsequently relapsed within a median of 38 days (range 8–180 days). In conclusion, quantification of WT1 may be used for MRD studies and for prognostification in AML.

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