Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1.
Hematologic malignancies such as acute and chronic myeloid leukemia are characterized by the malignant transformation of immature CD34(+) progenitor cells. Transformation is associated with elevated expression of the Wilm's tumor gene encoded transcription factor (WT1). Here we demonstrate that WT1 can serve as a target for cytotoxic T lymphocytes (CTL) with exquisite specificity for leukemic progenitor cells. HLA-A0201- restricted CTL specific for WT1 kill leukemia cell lines and inhibit colony formation by transformed CD34(+) progenitor cells isolated from patients with chronic myeloid leukemia (CML), whereas colony formation by normal CD34(+) progenitor cells is unaffected. Thus, the tissue-specific transcription factor WT1 is an ideal target for CTL-mediated purging of leukemic progenitor cells in vitro and for antigen-specific therapy of leukemia and other WT1-expressing malignancies in vivo.
Gao
L
L
Department of Immunology, Imperial School of Medicine, Hammersmith Hospital, London, UK.
Bellantuono
I
I
Elsässer
A
A
Marley
S B
SB
Gordon
M Y
MY
Goldman
J M
JM
Stauss
H J
HJ
D000328:Adult; D000941:Antigens / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis*; D015153:Blotting, Western; D016465:Bone Marrow Purging / Q000379:methods*; D002648:Child; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology*; D016162:Genes, Wilms Tumor; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014157:Transcription Factors / Q000032:analysis / Q000276:immunology*; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins
D000941:Antigens; D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins