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Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia
K Inoue, H Ogawa, Y Sonoda, T Kimura, H Sakabe, Y Oka, S Miyake, H Tamaki, Y Oji, T Yamagami, T Tatekawa, T Soma, T Kishimoto and H Sugiyama
Department of Medicine III, Osaka University Medical School, Japan.
To clarify whether the expression of the WT1 gene in leukemic cells is
aberrant or merely reflects that in normal counterparts, the expression
levels of the WT1 gene were quantitated for normal hematopoietic progenitor
cells. Bone marrow (BM) and umbilical cord blood (CB) cells were
fluorescence-activated cell sorting (FACS)-sorted into CD34+ and CD34- cell
populations, and the CD34+ cells into nine subsets (CD34+ CD33-, CD34+
CD33+, CD34+ CD38-, CD34+ CD38+, CD34+ HLA-DR-, CD34+ HLA- DR+, CD34+
c-kit(high), CD34+ c-kit(low), and CD34+ c-kit-) according to the
expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute
myeloid leukemic cells were also FACS-sorted into four populations (CD34+
CD33-, CD34+ CD33+, CD34- CD33+, and CD34- CD33-). FACS-sorted normal
hematopoietic progenitor and leukemic cells and FACS- unsorted leukemic
cells were examined for the WT1 expression by quantitative reverse
transcriptase-polymerase chain reaction. The WT1 expression in the CD34+
and CD34- cell populations and in the nine CD34+ subsets of BM and CB was
at either very low (1.0 to 2.4 x 10(-2)) or undetectable (< 10(-2))
levels (the WT1 expression level of K562 cells was defined as 1.0), whereas
the average levels of WT1 expression in FACS-sorted and -unsorted leukemic
cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels in normal
hematopoietic progenitor cells were at least 10 times less than those in
leukemic cells. Therefore, we could not find any normal counterparts of BM
or CB that expressed the WT1 at levels comparable with those in leukemic
cells. These results indicate an aberrant overexpression of the WT1 gene in
leukemic cells and imply the involvement of this gene in human
leukemogenesis.
Volume 89,
Issue 4,
pp. 1405-1412,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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