Follow-Up of Minimal Residual Disease in Acute Childhood Lymphoblastic Leukemia by WT1 Gene Expression in the Peripheral Blood: The Hungarian Experience

Abstract

The aim of the study was to investigate if monitoring WT1 gene expression in the peripheral blood is an appropriate approach to monitor the progression of childhood acute lymphoblastic leukemia (ALL). Forty-six patients have been enrolled into this study (24 ALL and 22 control, nonleukemic cases). The peripheral blood was tested for WT1 gene expression using a sensitive nested RT-PCR technique. The assay was sensitive enough to detect 10 2 leukemic cells among 10 6 normal leukocytes. In agreement with the literature 96% of childhood ALL (23/24) expressed WT1 independent of the prognostic factors of the disease. On the other hand, no WT1 gene expression was found in the peripheral blood of nonleukemic hematological diseases, except myelodysplasia. WT1 became negative in the peripheral blood of these patients at the end of the induction phase of the therapy in the majority of the cases (19/24), whereas clinical remission was achieved in all patients except one. WT1 gene expression changes in the peripheral blood was monthly monitored in 20 ALL patients for 1 year and in 16 cases during the second year (for a maximum of 21 months). Although continuous monitoring detected transient (1- to 3-month long) WT1 expression in the majority of the ALL cases (16/20), clinical relapse occurred in 2 cases only when the WT1 expression was maintained for 11-15 months. Follow up studies of the WT1 gene expression in the peripheral blood of WT1-positive childhood ALL may enable researchers to monitor MRD and detect a very low leukemic cell count (perhaps called "molecular relapse"). According to this study, the transient WT1 positivity for 1-3 months does not predict clinical relapse of childhood ALL, unlike a longer-lasting positivity.