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Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor
chimeric transgenes for terminal differentiation coupled to growth arrest
and apoptosis
M Selvakumaran, D Liebermann and B Hoffman-Liebermann
Department of Biochemistry and Biophysics, University of Pennsylvania
School of Medicine, Philadelphia 19104-6059.
Conditional mutants of the myeloblastic leukemic M1 cell line, expressing
the chimeric mycer transgene, have been established. It is shown that M1
mycer cells, like M1, undergo terminal differentiation coupled to growth
arrest and programmed cell death (apoptosis) after treatment with the
physiologic differentiation inducer interleukin-6. However, when
beta-estradiol is included in the culture medium, M1 mycer cells respond to
differentiation inducers like M1 myc cell lines, where the differentiation
program is blocked at an intermediate stage. By manipulating the function
of the mycer transgene product, it is shown that there is a 10-hour window
during myeloid differentiation, from 30 to 40 hours after the addition of
the differentiation inducer, when the terminal differentiation program
switches from being dependent on c-myc suppression to becoming c-myc
suppression independent, where activation of c-myc has no apparent effect
on mature macrophages. M1 mycer cell lines provide a powerful tool to
increase our understanding of the role of c-myc in normal myelopoiesis and
in leukemogenesis, also providing a strategy to clone c-myc target genes.
Volume 81,
Issue 9,
pp. 2257-2262,
05/01/1993
Copyright © 1993 by The American Society of Hematology
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