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Proliferation of normal and malignant human immature lymphoid cells
D Campana and G Janossy
Department of Immunology, Royal Free Hospital School of Medicine, London,
UK.
In this study, the proliferative activity of human B and T cell precursors
in central lymphoid organs, acute lymphoblastic leukemia (ALL) cells, and
permanent cell lines was investigated with double- and
triple-color-labeling methods for the analysis of cell cycle-associated
features such as 5-bromo-2'-deoxyuridine (BrdU) incorporation and the
expression of a nuclear proliferation-associated antigen, Ki67, together
with the phenotypic profile of the cells. In infant and regenerating bone
marrow (BM), 41.5% +/- 4.0% of terminal deoxynucleotidyl transferase (TdT+)
cells were Ki67+, and 30.0% +/- 4.0% incorporated BrdU. A similar
proportion of TdT+ dividing cells was observed in adult BM. The
proliferative activity of the B cell progenitors reached the peak at the
pre-B stage: 80.8% +/- 7.6% and 35.3% +/- 6.1% of c mu +, RFB7- cells were
Ki67+ and BrdU+, respectively. In contrast, greater than 95% of surface
immunoglobulin- positive BM lymphocytes were resting cells. In infant
thymus the highest dividing capacity (95% Ki67+, 60% to 90% BrdU+) was
observed in large cortical thymocytes (TdT+, CD1-, cCD3+), and TdT+, CD1+
cortical thymocytes also showed a high proliferative activity (74.3% +/-
2.3% Ki67+, 22.0% +/- 1.0% BrdU+), but TdT-, mCD3+ thymic lymphocytes were
mainly resting cells (less than 5% Ki67+, less than 1% BrdU+). The
proliferative activity of null and common ALL blasts was significantly
lower than that of normal BM TdT+ cells (15.5% +/- 4.2% Ki67+, 6.2% +/-
2.1% BrdU+; P less than .001). Dividing ALL blasts were TdT+ and expressed
surface antigens detected by CD10 and/or CD19 antibodies. In T cell-ALL,
the percentages of Ki67+ and BrdU+ blasts were also lower than those found
in the corresponding normal immature thymocytes (13.0% +/- 3.1% and 2.4%
+/- 1.3%, respectively; P less than .001). Thus, ALLs derive from actively
proliferating lymphoid precursors but have a lower dividing capacity than
the corresponding normal cell types. In ALL cases with heterogeneous
expression of markers such as cmu and CD1, dividing blasts were distributed
among both negative and positive populations, thus indicating that blasts
with signs of differentiation also remain within the dividing pool.
Volume 71,
Issue 5,
pp. 1201-1210,
05/01/1988
Copyright © 1988 by The American Society of Hematology
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