International Journal of Cell Cloning, Vol 7, 68-91, Copyright © 1989 by AlphaMed Press
Origins and properties of hematopoietic growth factor-dependent cell lines
JN Ihle and D Askew
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Studies of the growth regulation, differentiation and transformation of
myeloid cells have been greatly facilitated by the availability of a
variety of hematopoietic growth factor-dependent cell lines. These cell
lines have been isolated from long-term bone marrow cultures and myeloid
tumors using interleukin 3 (IL-3) as a growth factor. Using growth
factor-dependent cells, it has been shown that growth regulation by IL-3
involves binding to a high-affinity receptor of 140 Kd and activation of
tyrosine phosphorylation. IL-3 binding is associated with a number of
cellular responses which are required for maintenance of viability,
including induction of transcription of the c-myc and ornithine
decarboxylase (ODC) genes. In addition, IL-3 regulates the expression of
transcription of the gamma T cell receptor locus. The properties of the
IL-3-dependent lines are consistent with the hypothesis that they are
transformed in their ability to terminally differentiate. In some of the
cell lines, this transformation may terminally differentiate. In other of
the cell lines, this transformation may be due to the altered expression of
the c-myb gene. In other cell lines, transformation is associated with the
activation of the expression of a novel gene, termed Evi-1, of the zinc
finger family of transcriptional factors. Comparable transformation of
erythroid lineage cells is speculated to be due to the activation of the
expression of another novel gene termed spi-1. These studies have
emphasized the value of well-characterized hematopoietic growth factor-
dependent cell lines in advancing our understanding in the basic biology of
myeloid cells.
