Loss of myeloid differentiation antigens precedes blastic transformation in chronic myelogenous leukemia.
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)
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism*; D001752:Blast Crisis / Q000276:immunology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis; D006651:Histocytochemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D007951:Leukemia, Myeloid / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000939:Epitopes; C046168:neutrophil differentiation antigens