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Expression of the Wilms' Tumor Suppressor Gene, WT1, Is
Upregulated by Leukemia Inhibitory Factor and Induces Monocytic
Differentiation in M1 Leukemic Cells
Shirley I. Smith,
Dominique Weil,
Gregory R. Johnson,
Andrew W. Boyd, and
Chung L. Li
From the Queensland Institute of Medical Research (QIMR), Royal
Brisbane Hospital, Herston, Queensland, Australia.
The Wilms' tumor gene, WT1, encodes a transcription factor
of the Cys2-His2 zinc finger type. The
functional significance of WT1 expression in leukemias, in
addition to tissues and cell lines of hematopoietic origin, has not
been determined. Using the murine myeloblastic leukemia cell line M1 as
a model for macrophage differentiation, expression of WT1 is
shown to be activated in M1 cells 24 hours after differentiation
induction by leukemia inhibitory factor (LIF). Upregulation of
WT1 in these cells is associated with cellular differentiation,
coinciding with expression of the monocyte/macrophage marker
c-fms, and the appearance of mature cells. WT1 isoforms lacking
the KTS insert are unable to be ectopically expressed in M1 cells.
Stable expression of the WT1 isoforms containing the KTS insert leads
to spontaneous differentiation of the M1 myeloblasts through the
monocytic differentiation pathway. These cells express c-fms,
in addition to the myeloid-specific cell surface marker Mac-1. Exposure
of these cells to LIF results in the rapid onset of terminal macrophage
differentiation, accompanied by apoptotic cell death. These results
show that the WT1 gene is an important regulator of M1 cell
monocytic differentiation in vitro, and suggests a potential
role for this gene in the molecular control of hematopoiesis.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 764-773
© 1998 by The American Society of Hematology.
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