Asynchronous expression in B lineage acute lymphoblastic leukemia

Johns Hopkins Oncology Center, Pediatric Oncology, Baltimore, MD 21205.
Blood (Impact Factor: 10.45). 08/1988; 72(1):299-307.
Source: PubMed


Cell surface phenotypes of 113 B lineage acute lymphocytic leukemia (ALL) cases, defined by the presence of HLA-DR and at least one B-cell-specific antigen (either CD19, CD20, or CD22), were compared with antigen-defined stages of normal B lymphocyte development. The cases were first evaluated for expression of HLA-DR, CD19, CD34, CD10, CD20, and CD22 by indirect one-color immunofluorescence. Pairwise comparisons of cell surface marker expression were performed for each leukemic sample: no correlations were observed for paired antigen expression on the leukemic samples using antigens expressed either early or late during normal B lymphoid development. Complete immunophenotypes of the cases were then compared with normal B-cell developmental stages. Sixteen different complete immunophenotypes were observed on the leukemias that were not found in normal marrow; at least 78% of the cases demonstrated such "asynchronous" combinations of B lymphoid-associated differentiation antigens. Several samples were subsequently studied by two-color immunofluorescence, and the presence of doubly labeled cells with "asynchronous" antigen combinations was confirmed. These results indicate that the majority of B lineage leukemias exhibit "developmental asynchrony," as compared with normal marrow B cells. The data further suggest that ALL cases do not accurately represent cells arrested at the stage where the leukemogenic event occurred. Rather, ALL appears to be a disease in which there may be maturation of leukemic blasts; but this maturation is "asynchronous" when compared with the normal developmental process.

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Available from: Judith E Karp, Nov 23, 2014
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    • "Therefore the strategy for MRD detection in B-ALL is less straightforward than T-ALL. The use of PB for the detection of MRD is debatable because subtle leukaemia-associated deregulation of gene expression extends to many other molecules normally expressed during B-cell differentiation [33,34]. However two studies [35,36] have shown that paired MRD values in BM and PB are highly concordant in T-ALL. "
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    • "More recently, expression of characteristic myeloid antigens has been associated with distinct genetically defined subgroups (Borowitz et al, 1991; Griesinger et al, 1994; Lenkei et al, 1991; Ludwig et al, 1993, 1994). Other leukaemiaassociated immunophenotypes include asynchronous expression of maturational stage-associated antigens in Blineage ALL (Hurwitz et al, 1989), ectopic expressions of antigens in T-lineage ALL (van Dongen et al, 1993; Campana et al, 1991), aberrant antigen expression of B-and T-lineage associated antigens in leukaemic samples of the respective other lymphoid lineage (Grü mayer et al, 1991; Uckun et al, 1989; Muraguchi et al, 1992), and loss or low expression of common surface antigens such as CD45 in B-lineage ALL (Behm et al, 1992). Besides the pretherapeutic characterization of ALL, aberrant and asynchronous antigen expression may potentially be used for detection of persistent cells with LAIP in haematological complete remission (CR), termed minimal residual disease (MRD). "
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    ABSTRACT: Analysis of differentiation antigens on leukaemic blasts is routinely done for diagnostic purposes, i.e. determination of stage of differentiation and lineage assignment. Acute lymphoblastic leukaemias are also frequently characterized by a leukaemia-associated immunophenotype (LAIP), either the coexpression of differentiation antigens physiologically restricted to other stages of differentiation (asynchronous LAIP) or cell lineages (aberrant LAIP). We defined LAIP in 241 consecutive unselected B-lineage (n = 193) and T-lineage (n = 48) ALL by three-colour flow cytometry using directly conjugated monoclonal antibodies. The incidence of LAIP was found to be 91.7%. In 63% of patients two to six leukaemia-associated expression patterns were detected. In order to study the specificity of LAIP in a therapy-relevant setting, remission bone marrow samples from patients with B-lineage ALL were analysed for the expression of T-lineage-associated phenotypes on the normal bone marrow cells and vice versa. The frequency of all T-lineage LAIP+ cells and all aberrant B-lineage LAIP+ cells was <1% in regenerating bone marrow samples at different timepoints. The incidence and clinical significance of LAIP+ cells was studied in 196 remission marrows of 70 ALL patients (55 remaining in CCR, 14 with bone marrow relapse, one with isolated CNS relapse). The presence of >1% LAIP+ at two consecutive timepoints predicted 5/8 bone marrow relapses in B-lineage ALL. The occurrence of LAIP+ cells >1% in T-lineage ALL after induction therapy predicted relapse in 7/7 cases. In conclusion, flow cytometric detection of LAIP+ cells appears to be a powerful tool for the prediction of outcome in ALL.
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