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Clinical and biologic relevance of immunologic marker studies in childhood
acute lymphoblastic leukemia
CH Pui, FG Behm and WM Crist
Department of Hematology-Oncology, St Jude Children's Research Hospital,
Memphis, TN.
Immunologic marker studies of the lymphoid leukemias have greatly improved
the precision of diagnosis of these disorders by providing specific
information regarding the lineage and stage of maturation of the malignant
cells. Such studies have also enhanced our understanding of normal
lymphocyte development, permitting reproducible identification of lymphoid
cells in discrete developmental stages. By elucidating the functions of
lymphoid cell differentiation antigens, it has been possible to gain
insight into the signal transduction mechanisms by which these cells
interact among themselves and with other cell types. Similar studies have
shown that ALL is an immunophenotypically heterogeneous disease with
clinically important subtypes representing clonal expansions of
lymphoblasts at different stages of maturation. Furthermore, successful
correlation of immunophenotype with certain karyotypic and molecular
abnormalities, which appear to underlie most or all leukemias, were made
possible by the inclusion of immunologic marker assessment. Interestingly,
many of these phenotype-related abnormalities have involved either the Ig
or TCR genes, thus providing additional clues to the mechanisms of
leukemogenesis. Knowledge of the immunologic features of leukemic cells has
been essential for the generation of phenotype-specific response data in
the context of modern therapy for ALL. With wider use of intensive
treatment, the traditional prognostic distinctions among immunophenotypes
have begun to disappear; however, certain classes of agents have more
favorable toxicity/efficacy ratios against some immunophenotypes than
others, justifying continued efforts to target therapy by immunologic
species of ALL. Antibody-toxin conjugates, or immunotoxins, have induced
complete responses in preliminary trials and may prove clinically useful,
perhaps in combination with chemotherapy, if their toxic side effects can
be controlled. Finally, immunologic markers may serve as sensitive targets
for the detection of minimal residual disease; the clinical usefulness of
this approach will depend on prospective comparisons with molecular
methods.
Volume 82,
Issue 2,
pp. 343-362,
07/15/1993
Copyright © 1993 by The American Society of Hematology
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