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Biphenotypic leukemic lymphocyte precursors in CD2+CD19+ acute
lymphoblastic leukemia and their putative normal counterparts in human
fetal hematopoietic tissues
FM Uckun, A Muraguchi, JA Ledbetter, T Kishimoto, RT O'Brien, JS Roloff, K Gajl- Peczalska, A Provisor and B Koller
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis 55455.
During detailed immunophenotypic analyses of marrow blasts from 336 acute
lymphoblastic leukemia (ALL) patients, a very small percentage of cases
reactive with B-cell-directed as well as T-cell-directed monoclonal
antibodies (MoAbs) were identified. Five ALL cases were biphenotypic since
they coexpressed CD2 (Tp50) and CD19 (Bp95) antigens at the single-cell
level. The composite immunophenotype of these biphenotypic ALL cases was
[TdT+HLA-ABC+CD2+CD3-CD10+CD13-CD14-CD16- CD19+CD20+
++-CD21-CD33-CD34+Bgp95-C mu- slg-]. Low-molecular-weight B- cell growth
factor (LMW-BCGF), recombinant interleukin-2 (rIL-2), and rIL-3 stimulated
the proliferative activity of biphenotypic leukemic lymphocyte precursors
without inducing differentiation. In the presence of the phorbol ester TPA,
leukemic blasts from two cases differentiated along the B precursor pathway
to the [CD2-CD10+CD19+CD20+C mu+slg-] pre- B cell stage. Biphenotypic ALL
cases did not share a common configuration and gene rearrangement pattern
of the immunoglobulin heavy chain genes or T-cell receptor (TCR) genes.
Three cases had rearranged C mu genes but germline TCR genes, one case
showed rearrangement of both C mu and TCR genes, and the remaining case had
rearranged TCR genes but germline C mu genes. All five patients attained
prompt remission after standard induction chemotherapy. Three to four years
after initial diagnosis, four patients are now off chemotherapy and remain
alive in their first remission. One patient relapsed at 3 years, 7 months,
but promptly achieved complete remission after reinduction chemotherapy and
remains in second remission off chemotherapy greater than 3 years after her
reinduction therapy. With two-color immunofluorescence staining techniques
and multiparameter flow cytometric analyses, we identified a small
population of CD2+CD19+ lymphoid cells in fetal livers (FLs) and fetal bone
marrows (FBMs), which may represent the putative normal counterparts of
biphenotypic ALL blasts. A CD2+CD19+ normal biphenotypic lymphoid precursor
cell line, designated FL 8.2 CD2+, was established from an FL of 8-weeks of
gestational age by Epstein-Barr virus (EBV)-induced blastoid
transformation. The composite immunophenotype of FL 8.2 CD2+ cell line was
[TdT+HLA-ABC+HLA-DR+ CD2+CD5-CD7-CD10+/-CD13-CD19+CD20-CD21+
CD22+CD33-CD34+/-Bgp95-CDw40+C mu-slgD-slgM-]. FL 8.2 CD2+ cells showed
germline patterns of immunoglobulin heavy-chain joining region, heavy-
chain constant region, kappa light-chain constant region genes, and TCR
beta-chain genes. Cross-linking of CD2 as well as CD19 antigens on FL 8.2
CD2+ cells caused an increase of intracellular ionized calcium.(ABSTRACT
TRUNCATED AT 400 WORDS)
Volume 73,
Issue 4,
pp. 1000-1015,
03/01/1989
Copyright © 1989 by The American Society of Hematology
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