THE WILMS-TUMOR GENE IS FREQUENTLY EXPRESSED IN ACUTE MYELOBLASTIC LEUKEMIAS AND MAY PROVIDE A MARKER FOR RESIDUAL BLAST CELLS DETECTABLE BY PCR

Background: The tumor suppressor gene wt-1 was isolated by cytogenetic deletion analysis of patients with Wilms' tumor (wt-1). This gene enc odes for a zinc finger DNA-binding protein with transcription-repressi ng properties. During normal ontogenesis it is expressed in a time-and tissue-dependent manner mainly in the kidneys and gonads. Recently, t he expression of wt-1 in acute leukemias (AL) was reported. Here we in vestigated the prognostic potential of wt-1 mRNA expression during the course of the disease using the PCR technique. Patients and methods: Blast cells from 83 patients with newly diagnosed AML and 20 AML patie nts during followup in complete remission were analyzed for wt-1 mRNA expression. Peripheral blood mononuclear cells (PBMNC) and bone marrow (BM) from healthy persons (n = 13) and sorted CD34-positive cells fro m normal donors (n = 4) were used as negative controls. Results: Wt-1- specific m-RNA was detectable in 67/83 (81%) patients with AML. Normal donors did not express wt-1 m-RNA but in 1/4 sorted CD34+ cell sample s a weak amplified product was observed. After achieving cytological C R 14/20 studied patients lost wt-1 expression. In 7/8 patients in morp hological CR the reappearance of wt-1 expression preceded relapse of t he disease, in 1/8 patients wt-1 remained positive in CR. Response to therapy, disease free survival, overall survival and FAB-subtype did n ot correlate with wt-1 m-RNA expression in newly diagnosed AML before therapy. Conclusions: In the majority of acute leukemias wt-1 is expre ssed and probably blast cell-associated, at least in levels detectable by PCR. Wt-1 mRNA was detectable in bone marrow cells of AML patients in clinical CR. The results strongly suggest that the persistance or reappearance of wt-1 predicts relapse of the disease prior to morpholo gical relapse.