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Induction of differentiation in blast cells and leukemia colony-forming
cells from patients with acute myeloid leukemia
AL Howell, TA Stukel, CD Bloomfield, FR Davey and ED Ball
Department of Medicine, Dartmouth Medical School, Hanover, NH 03756.
The characteristic lesion in acute myeloid leukemia (AML) is the failure of
myeloid cells to differentiate normally, leading to the accumulation of
immature blast cells (BC) in the bone marrow. We determined whether BC and
leukemia colony-forming cells (L-CFC) from AML patients could differentiate
in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25
dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha
(TNF alpha), and granulocyte- monocyte colony-stimulating factor (GM-CSF).
Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124
was determined on the BC by immunofluorescence and on the L-CFC by
monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity
followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases
demonstrated changes in the expression of myeloid differentiation antigens
on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen
phenotype after short-term culture with differentiating agents. Alterations
in myeloid antigen expression in the L-CFC population correlated with a
reduction in L-CFC cloning potential. In the BC, alterations of myeloid
differentiation antigens occurred in a manner consistent with those
observed during normal myelopoiesis. For example, CD14 antigen expression
(a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases,
and p124 (an antigen expressed both by myeloid progenitor cells and by a
subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the
expression of CD33 antigens (expressed normally by myeloid progenitor cells
and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%)
showing a decrease and 7 of 29 cases (24%) showing an increase. When
comparisons were made between pairs of differentiation agents that caused
the altered expression of an antigen on either the BC or L-CFC of a
patient, the majority of changes were in the same direction (either both
"increased" or both "decreased"). This suggests that the direction of
antigen change is characteristic of the leukemia cell subpopulation for
each patient and not of the stimulatory agent. This study demonstrates that
cells from more than two thirds of AML cases examined responded to various
differentiation agents in vitro as measured by changes in the expression of
myeloid cell-associated surface antigens and by alterations in cloning
potential of the L-CFC, a finding of potential clinical significance.
Volume 75,
Issue 3,
pp. 721-729,
02/01/1990
Copyright © 1990 by The American Society of Hematology
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