PRESENCE OF WILMS-TUMOR GENE (WT1) TRANSCRIPTS AND THE WT1 NUCLEAR-PROTEIN IN THE MAJORITY OF HUMAN ACUTE LEUKEMIAS

The wt1 gene is located on chromosome 11p13 and encodes a zinc finger motif-containing transcription factor involved in regulation of growth and differentiation. Its expression was shown during embryonic develo pment in various tissues as well as in a few human malignancies includ ing acute leukemias. Using RT-PCR, we found wt1 gene expression in bla st cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) prepre-B-ALL patien ts, in 33 of 41 (80%) cALL patients, in 23 of 31 (74%) T-ALL patients, and in 53 of 57 (93%) AML patients. Additionally, mononuclear cells f rom CML patients expressed the wt1 gene only when diagnosed with blast crisis. In contrast to acute human leukemias, mononuclear cells from reactive bone marrow (n = 4), and peripheral blood of healthy voluntee rs (n = 20), as well as normal peripheral CD34(+) hematopoietic progen itors (n = 6) did not express the wt1 gene at detectable levels. Using the anti-WT1 MoAb 6F-H2 in an immunofluorescence assay on single cell level, we found the translated WT1 protein only in nuclei of leukemia blast cells but not in nuclei of normal CD34(+) hematopoietic progeni tor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nucl ear immunofluorescence. Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34(+) hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan -acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in p urged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.