Wilms Tumor Gene (WT1) as a New Marker for the Detection of Minimal Residual Disease in Leukemia

Abstract

WT1 (Wilms tumor gene) expression is a new tumor marker of leukemic blast cells of AML, ALL, and CML. Minimal residual disease (MRD) of leukemia can be detected at frequencies as low as 1 in 103 to 104 normal bone marrow (BM) cells and 1 in 105 normal peripheral blood (PB) cells by means of the quantitation of expression levels of the WT1 gene using reverse transcriptase-polymerase chain reaction (RT-PCR). This is regardless of the types of leukemia or the presence or absence of tumor-specific DNA markers. Thus, the WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cells in individual leukemia patients. Moreover, molecular relapse using PCR can be diagnosed by the monitoring of WT1 expression levels in BM or PB 1–24 months (means, 7 months for BM and 8 months for PB) before the clinical relapse became apparent. In case of rapid or gradual increase in WT1 expression levels to or over 10-2 after return to normal BM levels during CR; or retention of the WT1 expression at levels near or over 10-2 in BM without return to normal BM levels even in CR (WT1 expression level in K562 cells was defined as 1.0), it seems that clinical relapse is impending. Since WT1 antisense oligomers inhibit the growth of leukemic cells, it is apparent that the WT1 gene plays an important role in leukemogenesis.