Lq. Gao et al., Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1, BLOOD, 95(7), 2000, pp. 2198-2203
Hematologic malignancies such as acute and chronic myeloid leukemia are cha
racterized by the malignant transformation of immature CD34(+) progenitor c
ells. Transformation is associated with elevated expression of the Wilm's t
umor gene encoded transcription factor (WT1), Here we demonstrate that WT1
can serve as a target for cytotoxic T lymphocytes (CTL) with exquisite spec
ificity for leukemic progenitor cells. HLA-A0201-restricted CTL specific fo
r WT1 kill leukemia cell lines and inhibit colony formation by transformed
CD34(+) progenitor cells isolated from patients with chronic myeloid leukem
ia (CML), whereas colony formation by normal CD34(+) progenitor cells is un
affected. Thus, the tissue-specific transcription factor WT1 is an ideal ta
rget for CTL-mediated purging of leukemic progenitor cells in vitro and for
antigen-specific therapy of leukemia and other WT1-expressing malignancies
in vivo. (Blood. 2000;95:2198-2203) (C) 2000 by The American Society of He
matology.