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 development in various tissues as well as in a few human malignancies including acute leukemias. Using RT-PCR, we found wt1 gene expression in blast cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) pre-pre-B-ALL patients, 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 from 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 volunteers (n = 20), as well as normal peripheral CD34+ hematopoietic progenitors (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 progenitor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nuclear 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 purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.
Menssen
H D
HD
Department of Hematology and Oncology, Benjamin Franklin Klinik, Freie Universität Berlin, Germany.
Renkl
H J
HJ
Rodeck
U
U
Maurer
J
J
Notter
M
M
Schwartz
S
S
Reinhardt
R
R
Thiel
E
E
D000328:Adult; D001483:Base Sequence; D001752:Blast Crisis; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D016162:Genes, Wilms Tumor; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025721:WT1 Proteins