Wilms' tumor 1 (WT1) gene in hematopoiesis: a surrogate marker of cell proliferation as a possible mechanism of action?
BACKGROUND
Wilms' tumor 1 (WT1) gene expression is seen in a significant number of cases of human neoplasia; however, the mechanism of action remains to be clarified. We hypothesized that WT1 gene is a surrogate marker of proliferation in normal hematopoietic cells and leukemias. While we and others have recognized its value as a tool for the detection of minimal residual disease (MRD), the objective of this study was to confirm our hypothesis regarding normal.


METHODS
Samples from healthy donors (n=16) and UC blood (n=9) were cultured in Methocult for 21 days. Colonies were analyzed on days 7, 14 and 21 by RT-PCR for WT1 gene expression. Our positive controls were samples from patients with leukemia (n=91). Negative controls were from normal volunteers without stimulation (n=26).


RESULTS
Results showed a statistically significant difference (P<0.0001) between cultured groups, with the highest level of WT1 gene expression in the positive controls and on day 14, when cells are at their maximal proliferation.


CONCLUSIONS
In conclusion, WT1 gene expression in the proliferating colonies was highest on day 14, although less than in leukemia samples, confirming our hypothesis that WT1 gene is a surrogate marker of proliferation, not only in leukemogenesis but also, to a lesser degree, in normal cell proliferation.
Olszewski
M
M
Stem Cell Processing, Children's Memorial Hospital, Chicago, Illinois 60614, USA.
Huang
W
W
Chou
P M
PM
Duerst
R
R
Kletzel
M
M
D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D016162:Genes, Wilms Tumor / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000175:diagnosis* / Q000235:genetics*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
D016207:Cytokines; D005819:Genetic Markers; D012333:RNA, Messenger; D025721:WT1 Proteins