Comparison of minimal residual disease (MRD) monitoring by WT1 quantification between childhood acute myeloid leukemia and acute lymphoblastic leukemia

摘要

OBJECTIVE: Wilms tumor gene 1 (WT1) has been identified as an independent risk prognostic factor in acute leukemia. However, there exists a controversy that WT1 as a marker for minimal residual disease (MRD) monitoring in acute leukemias. We detected WT1-RNA transcript level to estimate the diagnostic value of monitoring MRD in childhood acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: WT1 mRNA expression levels were detected by real-time quantitative reverse transcriptase PCR (qRT-PCR) in bone marrow (BM) samples from 107 childhood ALL and 35 childhood AML at diagnosis. MRD was consecutively performed after induction and consolidation (early intensification in ALL) chemotherapy. Receiver operating characteristics (ROC) analysis and the largest areas under the curve (AUC) were applied to define optimal threshold value of MRD level. Sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LR) were used to evaluate diagnostic power for MRD. Relapse free survival (RFS) was evaluated by the Kaplan-Meier statistical method. RESULTS: The largest areas under the curve (AUC), specificity, +LR and –LR showed higher accuracy in childhood AML than ALL. Compared the diagnostic parameters, the post-induction time wasn’t good enough to show the better time than post-consolidation time for MRD assessment in AML. The threshold was set at 150 WT1 copies/104 ABL copies as the optimal cut-off value of MRD level post induction in childhood AML. MRD+ (WT1>150) children had increased the risk of relapse with poor prognosis, showing lower RFS than MRD- group (p=0.01). However, the threshold 70 WT1 copies/104 ABL copies post induction in childhood ALL did not show clinical significance for predicting prognosis (p=0.056). CONCLUSIONS: WT1 gene will be a useful marker for monitoring MRD to predict relapse in childhood AML. But it did not show good enough to monitor MRD in childhood ALL.