title: Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34 overexpression in acute myelogenous leukemia M2 with t(8;21).
abstract: During the immunodiagnosis of 517 cases of acute myelogenous leukemia (AML) entered into the Medical Research Council (MRC) AML 10 trials, we have observed the CD34 precursor cell antigen more frequently in AML of M2 morphology, especially in the 84% of cases with the t(8;21) chromosomal translocation, than in any other French-American-British classification group. CD34 expression was then quantified (using QIFI and Quantum Simply Cellular beads [Flow Cytometry Standards, Research Triangle Park, NC] and CD34+ standard cells). When CD34 antibody-binding capacity (ABC) of normal bone marrow (BM) precursors and leukemic blasts was compared, it was shown that AML M2 cases with t(8;21) not only had the highest percentages of CD34+ blasts, but in > 80% of CD34+ cases the individual blasts expressed higher than normal levels of CD34 antigen (> 60 x 10(3) ABC per cell). In addition, in 73% of this group CD34 antigen was overexpressed in an asynchronous combination with cytoplasmic myeloperoxidase (MPO). Other signs of asynchrony included high CD34 expression with CD15 and/or CD56, as well as aberrant combinations of CD13 with terminal deoxynucleotidyl transferase (TdT) and CD19. These findings demonstrate that asynchrony is identifiable in virtually every case of AML with t(8;21), although it does not always involve the same antigens. M2 cases with t(8;21), mostly CD34+, had a 100% remission rate and 71% 5-year survival rate; other patients with CD34+ or CD34- AML showed 69% and 84% remission rates and 31% and 36% 5-year survival rates, respectively. Consequently, individual markers such as CD34 should be interpreted in relation to other features such as chromosomal changes. These simple methods, which are well suited to quantify the expression of ligands, are a useful contribution to diagnosis: 60% to 65% of M2 cases with t(8;21) are rapidly identified by CD34 overexpression alone. This aberration, together with the other signs of asynchrony seen at presentation, can be used to search for residual leukemia after therapy.
authors.affiliation: Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Porwit-MacDonald
authors.forename: G
authors.initials: G
authors.lastname: Janossy
authors.forename: K
authors.initials: K
authors.lastname: Ivory
authors.forename: D
authors.initials: D
authors.lastname: Swirsky
authors.forename: R
authors.initials: R
authors.lastname: Peters
authors.forename: K
authors.initials: K
authors.lastname: Wheatley
authors.forename: H
authors.initials: H
authors.lastname: Walker
authors.forename: A
authors.initials: A
authors.lastname: Turker
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: A
authors.initials: A
authors.lastname: Burnett
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000235:genetics; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D015331:Cohort Studies; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015993:Life Tables; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion