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Expression of the c-fgr and hck protein-tyrosine kinases in acute myeloid
leukemic blasts is associated with early commitment and differentiation
events in the monocytic and granulocytic lineages
CL Willman, CC Stewart, TL Longacre, DR Head, R Habbersett, SF Ziegler and RM Perlmutter
Department of Cell Biology, University of New Mexico School of Medicine,
Albuquerque 87131.
Two members of the src proto-oncogene family of intracellular tyrosine
kinases, c-fgr and hck, are selectively expressed in differentiated myeloid
cells. To study the expression of these genes in acute myeloid leukemia
(AML) and to determine the specific myeloid lineages and stages of myeloid
differentiation at which the expression of these genes is acquired, we used
a series of 79 cases of de novo AML as a differentiation model. The levels
of c-fgr, hck, and c-fms (encoding the colony-stimulating factor-1
receptor) mRNA transcripts were correlated with the presence of specific
cell surface antigens and the morphologic and cytochemical features in
these AML blasts. Relatively undifferentiated leukemic myeloblasts with an
HLA-DR, CD34, CD33, CD13+/- cell surface immunophenotype
(French-American-British [FAB] M1 or M2) were characterized by a lack of
c-fms and c-fgr expression, while low levels of c-fms and c-fgr could be
detected in undifferentiated myeloblasts (FAB M1 or M2), which also
expressed CD14 at low antigen density. The hck transcripts were either
undetectable in these cells or were expressed at low levels. In contrast,
only hck mRNA transcripts could be identified in blasts with
progranulocytic morphology (FAB M3), while c-fms, c-fgr, and hck were all
expressed at high levels in blasts with differentiated myelomonocytic or
monocytic features (FAB M4 and M5). No c-fms, c-fgr, or hck transcripts
were evident in leukemic cells of the erythroid lineage (FAB M6). When
undifferentiated leukemic myeloblasts (HLA-DR, CD34, and CD33) were induced
to differentiate in vitro to cells with monocytic characteristics, the
expression of c-fms, c-fgr, and the CD14 cell surface antigen were induced
to high levels, accompanied by the acquisition of hck and CD13 expression.
In contrast, when HLA-DR, CD34, and CD33 blasts were induced to
differentiate in vitro to cells with granulocytic characteristics, only hck
and CD13 expression were induced. Our data suggest that the acquisition of
c-fgr and/or hck expression is associated with early commitment and
differentiation events in distinct myeloid lineages. Assessment of the
expression of these kinases may provide a molecular tool to assign lineage
in AML in conjunction with morphology, cytochemistry, and cell surface
antigen expression.
Volume 77,
Issue 4,
pp. 726-734,
02/15/1991
Copyright © 1991 by The American Society of Hematology
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