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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4317-4324
Flow Cytometric Diagnosis of the Cell Lineage and Developmental Stage
of Acute Lymphoblastic Leukemia by Novel Monoclonal Antibodies Specific
to Human Pre-B-Cell Receptor
Keiko Tsuganezawa,
Nobutaka Kiyokawa,
Yoshinobu Matsuo,
Fujiko Kitamura,
Noriko Toyama-Sorimachi,
Keisuke Kuida,
Junichiro Fujimoto, and
Hajime Karasuyama
From the Department of Immunology, The Tokyo Metropolitan Institute
of Medical Science, Tokyo; Biomedical R&D Department, Sumitomo Electric
Industries, Ltd, Yokohama; the Department of Pathology, National
Children's Medical Research Center, Tokyo; and Fujisaki Cell Center,
Hayashibara Biochemical Labs Inc, Okayama, Japan.
Three novel monoclonal antibodies (MoAbs) have been
established that recognize distinct epitopes of a human pre-B-cell
receptor (pre-BCR) composed of a µ heavy (µH) chain and a
 5/VpreB surrogate light (SL) chain. HSL11 reacts with 5 whereas
HSL96 reacts with VpreB. Intriguingly, HSL2 does not bind to each
component of the pre-BCR but does bind to the completely assembled
pre-BCR complex. Flow cytometric analyses with cytoplasmic staining of
a panel of human cell lines showed that HSL11 and HSL96 specifically
stained cell lines derived from the pro-B and pre-B-cell stages of
B-cell development. In contrast, HSL2 stained exclusively cell lines derived from the pre-B-cell stage. These results prompted us to explore the possibility of clinical application of these MoAbs for the
determination of the cell lineage and developmental stage of acute
lymphoblastic leukemia (ALL). Whereas none of mature B-lineage ALLs
(B-ALLs), T-lineage ALLs (T-ALLs), and acute myeloid leukemias analyzed
were stained in the cytoplasm with these three MoAbs, the vast majority
of non-B- and non-T-ALLs (53 out of 56 cases) were found positive for
either 5, Vpre-B, or both in their cytoplasm. Among these 53 cytoplasmic SL chain-positive ALLs, 19 cases were also positive for
cytoplasmic µH chain, indicative of pre-B-cell origin.
Interestingly, 6 out of these 19 pre-B-ALL cases were found negative
for cytoplasmic staining with HSL2. From these results, we propose a
novel classification of B-ALL in which five subtypes are defined on the
basis of the differential expression of SL chain, µH chain, pre-BCR,
and light chain along the B-cell development.
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