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The expression pattern of erythrocyte/megakaryocyte-related transcription
factors GATA-1 and the stem cell leukemia gene correlates with
hematopoietic differentiation and is associated with outcome of acute
myeloid leukemia
T Shimamoto, K Ohyashiki, JH Ohyashiki, K Kawakubo, T Fujimura, H Iwama, S Nakazawa and K Toyama
First Department of Internal Medicine, Tokyo Medical College, Japan.
To understand the clinical implications of transcription factors and their
biologic roles during cellular differentiation in the hematopoietic system,
we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL)
gene in human leukemia cell lines and various leukemia patients using the
reverse transcriptase-polymerase chain reaction. Cell lines exhibiting
megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene
transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2,
or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not
SCL gene expression, was detected; GATA-1 expression in HL-60 cells was
downregulated during the process of monocytic differentiation. We next
examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples
obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute
lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast
crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1
expression and was preferentially detected in patients with leukemia
exhibiting megakaryocytic or erythrocytic phenotypes, while patients with
monocytic leukemia were clustered in the group with no detectable GATA-1
expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL.
De novo AML patients with SCL gene expression had a lower complete
remission (CR) rate and had a significantly poorer prognosis. Among the
patients with AML not expressing SCL, a high percentage of patients with
CD7+ AML and CD19+ AML had detectable GATA-1, while patients with
GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that
the expression pattern of transcription factors reflects the lineage
potential of leukemia cells, and GATA-1 and SCL gene expression may have
prognostic value for the outcome of patients with AML.
Volume 86,
Issue 8,
pp. 3173-3180,
10/15/1995
Copyright © 1995 by The American Society of Hematology
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