c-sis but not c-fos gene expression is lineage specific in human myeloid
cells
E Sariban, T Mitchell, A Rambaldi and DW Kufe
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston,
MA 02115.
Expression of both the c-fos and c-sis protooncogenes during myeloid
differentiation has been detected in cells of the monocytic lineage. Since
an increase in c-fos transcripts was not detected during dimethylsulfoxide
induced HL-60 granulocytic differentiation, it was suggested that within
the myeloid series c-fos gene expression might be lineage specific. In the
present study, we have determined whether expression of the c-fos and c-sis
genes is indeed specific for the monocytic pathway or rather common to both
the granulocyte and monocyte pathways. C-fos and c-sis gene expression was
analyzed in freshly isolated human granulocytes and monocytes, in human
HL-60 promyelocytic leukemia cells induced to differentiate along the
granulocytic or monocytic pathway, in myeloblasts from five patients with
the M1 or M2 subtype of acute myeloblastic leukemia (AML) and in blasts
from six patients with M4 myelomonocytic leukemia. The level of c-fos mRNA
was fifteen times higher in granulocytes as compared with monocytes. An
increase in c-fos expression was also found in HL-60 cells differentiated
along the granulocytic pathway after exposure to hypoxanthine,
hexamethylene bisacetamide, and the combination of retinoic acid and
dibutyryl adenosine 3'5' cyclic monophosphate. Three of 5 M1 and M2
leukemic myeloblast preparations depleted of lymphoid and monocytic cells
and all six M4 leukemic cells expressed c-fos transcripts. In contrast,
c-sis gene transcripts were detectable in monocytes and during drug induced
monocytic differentiation of the HL- 60 cells but not in granulocytes
during granulocytic differentiation of the HL-60 cells or in AML samples.
Thus, in the myeloid series, c-sis gene expression is lineage specific
while expression of the c-fos gene is found in both lineages and may be
related to metabolic pathways common to both granulocytes and monocytes.
Volume 71,
Issue 2,
pp. 488-493,
02/01/1988
Copyright © 1988 by The American Society of Hematology