Loss of myeloid differentiation antigens precedes blastic transformation in
chronic myelogenous leukemia
MB Todd, JA Waldron, TA Jennings, LS Rome, SD Markowitz, TR Holford, JP Gardner, JP Wolak and HL Malech
In order to determine whether antigenic patterns alter with disease
progression and are thereby suggestive of impending blast crisis in chronic
myelogenous leukemia, 50 bone marrow biopsy specimens from 32 patients were
examined retrospectively using indirect immunoperoxidase labeling with
three monoclonal antibodies that detect myeloid antigens. Monoclonal
antibodies PMN13F6, PMN7C3, and PMN8C7 detect human neutrophil antigens
that first appear at the myeloblast, promyelocyte, and metamyelocyte stages
of differentiation, respectively, and persist throughout later
differentiation. Percentages of antigen-positive bone marrow cells during
the chronic phase were compared with percentages of antigen-positive cells
at blast transformation, and time from bone marrow biopsy until blast
crisis was correlated with the percentage of bone marrow cells expressing
these antigens. Bone marrow biopsy samples from patients in the chronic
phase who continue to remain clinically stable 4 to 106 months after biopsy
expressed PMN13F6 antigen on 82% +/- 9% (mean +/- SD) of cells, PMN7C3
antigen on 62% +/- 14% of cells, and PMN8C7 on 68% +/- 14% of cells. Bone
marrow biopsy specimens obtained from patients 1 or more years prior to
blast transformation expressed PMN13F6 antigen on 81% +/- 12%, PMN7C3
antigen on 71% +/- 16%, and PMN8C7 on 64% +/- 16% of cells. Bone marrow
biopsy samples obtained between 2 months and 1 year prior to blast crisis
expressed PMN13F6 antigen on 68% +/- 15%, PMN7C3 on 51% +/- 17%, and PMN8C7
antigen on 46% +/- 18% of cells. Bone marrow biopsy specimens taken at the
time of blast transformation expressed PMN13F6 antigen on 20% +/- 25%,
PMN7C3 antigen on 19% +/- 25%, and PMN8C7 antigen on 13% +/- 25% of cells.
The difference between the mean of antigen-positive cells from bone marrow
biopsy samples obtained at the time of blast crisis was significant
compared with the mean of positive cells from biopsy specimens obtained at
all other phases of the disease (P less than .001 for all three
antibodies). There was a positive correlation between loss of myeloid
antigens and disease progression as determined by simple regression of log
time and correlation analysis (PMN13F6, r = .6533, P less than .005;
PMN7C8, r = .6304, P less than .005; PMN8C7, r = .5215, P less than .05).
There was a negative correlation between percentage of immature cells and
time to blastic crisis (r = -.6206, P less than .005).(ABSTRACT TRUNCATED
AT 250 WORDS)
Volume 70,
Issue 1,
pp. 122-131,
07/01/1987
Copyright © 1987 by The American Society of Hematology
