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Temporal association of CD40 antigen expression with discrete stages of
human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against
clonogenic B-lineage acute lymphoblastic leukemia as well as B- lineage
non-Hodgkin's lymphoma cells
FM Uckun, K Gajl-Peczalska, DE Myers, W Jaszcz, S Haissig and JA Ledbetter
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis 55455.
Detailed immunophenotypic analyses of immunologically classified leukemias
and lymphomas showed that CD40 displays an exquisite B- lineage specificity
within the human lymphopoietic system. Notably, 82% of B-lineage chronic
lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs),
86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute
lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the
correlated expression of CD40 and other B-lineage differentiation antigens
on fetal lymphoid precursor cells by multiparameter two-color/three-color
flow cytometry, combined with analyses of sequential antigen expression on
fluorescence- activated cell fluorescence activated cell sorter (FACS)
isolated immunologically distinct fetal B-cell precursor subpopulations
during in vitro proliferation and differentiation, provided evidence that
the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent
to the expression of CD10 and CD19 antigens but before the surface
expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM).
Some leukemic pro-B cells from ALL patients as well as normal pro-B cell
clones from fetal livers displaying germline Ig heavy chain genes were
CD40+, indicating that the acquisition of CD40 antigen likely precedes the
rearrangement of Ig heavy chain genes. CD40+ FACS- sorted malignant cells
from B-lineage ALL as well as B-lineage NHL patients were capable of in
vitro clonogenic growth, indicating the CD40 antigen is expressed on
clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by
the ability of an anti-CD40 immunotoxin that we used as an antigen-specific
cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
Volume 76,
Issue 12,
pp. 2449-2456,
12/15/1990
Copyright © 1990 by The American Society of Hematology
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