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Ambiguous phenotypes and genotypes in 16 children with acute leukemia as
characterized by multiparameter analysis
WD Ludwig, CR Bartram, J Ritter, A Raghavachar, W Hiddemann, G Heil, J Harbott, H Seibt-Jung, JV Teichmann and H Riehm
Department of Hematology/Oncology, Klinikum Steglitz, Berlin, FRG.
Ambiguous phenotypes and genotypes were observed in 16 children with acute
leukemia. Surface marker, cytogenetic, molecular genetic, and DNA flow
cytometric analyses as well as standard morphologic and cytochemical
studies were used to divide the patients into three groups. The first group
comprised five children with acute leukemia whose blast cells were
morphologically lymphoid, while immunophenotyping disclosed simultaneous
expression of early pre-B cell and myeloid features. Molecular genetic
studies showed evidence of heavy-chain immunoglobulin (Ig) gene
rearrangements in all patients. Cytogenetic data, available in three of
these children, revealed t(4;11). In five of the 16 patients, morphologic
and surface marker analyses indicated the coexistence of two separate cell
populations, one with myeloid and the other with early pre-B cell features.
Further evidence of B cell commitment in these patients was provided by
demonstration of Ig heavy-chain gene rearrangements in all five patients.
Surprisingly, one of the five patients showed oligoclonal Ig heavy-chain as
well as monoclonal gene rearrangement for the beta chain of the T cell
receptor (beta-TCR). The last group consisted of four cases with otherwise
typical acute lymphoblastic leukemia (ALL), early pre-B cell phenotype, and
coexpression of myeloid or T cell-associated antigens, and two children
with unequivocal acute myeloid leukemia (AML) and coexpression of T cell
antigens. Gene rearrangement of Ig heavy-chain could be demonstrated in
five of six patients, additional Ig light-chain gene rearrangement in two
children with ALL, and bigenotypic features (Ig heavy-chain and beta-TCR
gene rearrangement) in one patient. In none of the 16 patients did flow
cytometry disclose clonal abnormalities of leukemic cell DNA content. Based
on these findings, we suggest that malignant transformation in the first
and second group of patients took place at a stage ontogenetically close to
the pluripotent stem cell, whereas ambiguous phenotypes in the third group
resulted from aberrant gene expression or insufficient reagent specificity.
Volume 71,
Issue 6,
pp. 1518-1528,
06/01/1988
Copyright © 1988 by The American Society of Hematology
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