Cell surface markers in leukemia: biological and clinical correlations

Abstract

Recent advances in analysis of leukemic cell phenotypes using cell surface markers have provided important insights into leukocyte differentiation and the cellular origin of leukemia. In addition to the traditional cell surface markers, i.e., surface membrane immunoglobulin and receptors for sheep erythrocytes that define B and T lymphocytes, highly specific monoclonal antibodies have been developed that discriminate various stages of human lymphocyte and granulocyte differentiation. Explorations of the detailed phenotypes of leukemic cells in relation to normal hemopoietic differentiation reveal that consistent, composite phenotypes of different subclasses of lymphoid malignancies closely mimic those of corresponding normal cells at equivalent levels of maturation. This is exemplified in lymphoma cells (chronic lymphocytic leukemia of B or T type, Sezary Syndrome, immunocytoma) that resemble mature and immunocompetent T and B cells, in T cell acute lymphoblastic leukemia (T-ALL) (equivalent to thymus cells) and in non-T ALL (corresponding to lymphoid progenitor cells in the bone marrow). The major phenotypes documented in different leukemias represent the level of maturation arrest imposed on the dominant subclone; this is determined by, but not necessarily synonymous with, the target cell and associated clonogenic cell population in the leukemia. The clinical significance of immunodiagnosis of leukemia cell types becomes best evidenced in acute leukemias. Besides the improvement of diagnosis by using objective criteria, clinically useful subclassifications became evident: five major subtypes of ALL are now recognized, including unclassified or null ALL, common ALL, pre-B-ALL, B-ALL and pre-T/T-ALL. In addition to disclosing that ALL is an heterogeneous disease, such classifications have proved to be prognostically significant. This is exemplified in 248 children and 145 adults with ALL which were analysed for cell type and clinical data. In addition to their utility in leukemia classification, monoclonal antibodies that identify leukemia associated antigens are becoming used therapeutically, e.g., to lyse residual leukemia cells from remission bone marrows removed from leukemia patients before reinfusion. New approaches to the treatment of leukemia in which the objective is to encourage maturation of leukemia cells rather than to achieve leukemia eradication, can be monitored by phenotyping the alterations of the cell surface, and cell markers may hopefully be useful in identifying cell types that can be induced to differentiate.