ABERRANT OVEREXPRESSION OF THE WILMS-TUMOR GENE (WT1) IN HUMAN LEUKEMIA

To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expressi on levels of the WT1 gene were quantitated for normal hematopoietic pr ogenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells w ere fluorescence-activated cell sorting (FACS)-sorted into CD34(+) and CD34(-) cell populations, and the CD34(+) cells into nine subsets (CD 34(+)CD33(-) CD34(+)CD33(+), CD34(+)CD38(-), CD34(+)CD38(+), CD34(+)HL A-DR(-), CD34(+)HLA-DR(+), CD34(+)c-kit(high), CD34(+)c-kit(low), and CD34(+)c-kit(-)) according to the expression levels of CD34, CD33, CD3 8, HLA-DR, and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34(+)CD33(-), CD34(+)CD33(+), CD 34(-) CD33(+), and CD34(-)CD33(-)). FACS-sorted normal hematopoietic p rogenitor and leukemic cells and FACS-unsorted leukemic cells were exa mined for the WT1 expression by quantitative reverse transcriptase-pol ymerase chain reaction. The WT1 expression in the CD34(+) and CD34(-) cell populations and in the nine CD34(+) subsets of BM and CB was at e ither very low (1.0 to 2.4 x 10(-2)) or undetectable (<10(-2)) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas t he average levels of WT1 expression in FACS-sorted and -unsorted leuke mic cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less tha n those in leukemic cells. Therefore, we could not find any normal cou nterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpre ssion of the WT1 gene in leukemic cells and imply the involvement of t his gene in human leukemogenesis. (C) 1997 by The American Society of Hematology.