Cell cycle analysis in lymphoid neoplasia of childhood: differences among immunologic subtypes and similarities in the proliferation of normal and leukaemic precursor B cells.

Cell proliferation in untreated lymphoid malignancies of children was investigated by an in vitro assessment of the 3H-thymidine labelling index (LI), the growth fraction (GF) with the monoclonal antibody Ki-67, and the duration of the DNA-synthesis phase (ts) with a double labelling technique. Mean cell cycle time (tg) was similar in lymphoid malignancies of precursor B cell and T cell origin (115 h and 102 h, respectively), while B cell neoplasias had a mean tg of only 25 h. A positive correlation between the LI and the GF (r = 0.892) and a negative correlation between the LI and tg (r = -0.908) could be detected in childhood lymphoid malignancies. The proliferation of neoplastic precursor B cells was compared with the proliferation of presumably normal terminal transferase (TdT) positive bone marrow cells that, according to the immunophenotype, correspond mainly to normal precursor B cells. Although mean ts was identical in both cell populations (18-19 h), the neoplastic cell population showed a significantly longer mean tg than the normal counterpart (115 h and 65 h, respectively). However, if malignant and normal precursor B cell populations with a similar LI were compared, the difference in tg disappeared. Therefore, a down-regulation of leukaemic cell proliferation by an increasing cell mass is postulated for most cases of untreated precursor B cell ALL.