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Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1364-1373
Differential Binding Activity of the Transcription Factor LIL-Stat in
Immature and Differentiated Normal and Leukemic Myeloid Cells
Leonore M.L. Tuyt,
Krista Bregman,
Chantal Lummen,
Wim H.A. Dokter, and
Edo Vellenga
From the Division of Hematology and Center for Biomedical Technology,
University of Groningen, The Netherlands.
Cytokines and growth factors induce activation of the family of
signal transducers and activators of transcription (Stats) that
directly activate gene expression. Recently, constitutively activated
Stat1, Stat3, and Stat5 were identified in nuclear extracts of acute
myeloid leukemia (AML) patients, suggesting involvement of constitutive
Stat activity in the events of leukemogenesis. In the present study,
blasts of nine AML cases were investigated for the constitutive binding
activity of the recently identified transcription factor LIL-Stat (LPS-
and IL-1-inducible Stat). Band-shift assays were performed using the
LPS-and IL-1-responsive element (LILRE) oligonucleotide, a gamma
interferon activation site-like site that is present in
the human IL-1 promoter. Constitutive LIL-Stat binding activity was
observed in three leukemic cell lines and in seven out of nine AML
cases. Transient transfection studies with a reporter plasmid
containing three sequential LIL-Stat binding sites showed distinct
transcriptional activity of LIL-Stat only in those AML blasts that
constitutively expressed LIL-Stat. In CD34+ cells LIL-Stat also
constitutively bound to its consensus sequence. However, when these
cells were cultured in the presence of macrophage-colony stimulating
factor (M-CSF) and stem cell factor (SCF) for differentiation along the
monocytic lineage, the LIL-Stat binding activity disappeared totally.
In agreement with these findings neither mature monocytes nor
granulocytes showed constitutive or inducible LIL-Stat binding
activity. We conclude that the LIL-Stat transcription factor is
constitutively activated in undifferentiated and leukemic hematopoietic
cells, but not in mature cells. This may suggest a role for this
transcription factor in the process of differentiation.
© 1998 by The American Society of Hematology.
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