Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Abstract

The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia-related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in lo3 to lo4 cells.Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia-associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102).We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia. o 1992 Wiley-Liss, Inc.

A limited antibody panel can distinguish B-precursor acute lymphoblastic leukemia from normal B precursors with four color flow cytometry: implications for residual disease detection

“…Most of these studies have been based on the detection of cells expressing combinations of antigens not present on normal cells. 1,11,[34][35][36][37][38][39] Although essentially all T-ALL express abnormal phenotypes, 1 B-precursor ALL has provided more of a challenge because of the known similarities between leukemic phenotypes and those of normal B cell precursors. 42,47,48 Orfao et al 53 were able to distinguish normal and leukemic B cell precursors on the basis of myeloid antigen expression, but found that only 55% of a series of 56 patients had informative phenotypes.…”

BIOMED-1 Concerted Action report: Flow cytometric characterization of CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and follow-up of T cell acute lymphoblastic leukemia (T-ALL)

“…4 The aberrant immunophenotypic characteristics of leukemic T lymphoblasts allow discrimination from T cell subsets in BM and thus can be used for detection of minimal residual disease (MRD). [5][6][7][8] A comprehensive analysis of the immunophenotypic characteristics of T cells and the subsequent identification of all T cell subsets in normal BM are important for the reliable distinction between normal and leukemic T cells.…”

Clonal chromosomal abnormalities in the stem cell compartment of patients with acute myeloid leukemia in morphological complete remission

“…First studies show a correlation between the amount of aberrant cells and the remission duration. [25][26][27][28] The detection of minimal residual disease may hence be associated with clinical relapse in distinct subtypes of AML and quantification of MRD might be one decisive parameter for the choice of the adequate therapeutic strategy such as the use of unrelated allogenic transplant in patients with high MRD. So far it is not known in which hematopoietic cell compartment these residual leukemic cells reside.…”