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In 23 children with untreated precursor B-cell acute lymphoblastic leukaemia (ALL), the daily growth rate of the malignant cell clone was calculated. Cell birth expanded the leukaemic cell clone an average 10-11% per day, programmed cell death or apoptosis reduced the leukaemic cell mass by some 4% per day. From these two variables a net increase in the size of the leukaemic cell population of 6.9+/-7.3% (range -1.2-27.3%) per day could be calculated. The daily growth rate correlated negatively with the logarithm of the duration of clinical symptoms before the diagnosis of ALL was established (r=-0.680; P=0.0004). A long history, especially in children with undefined bone pain and arthralgias, was associated with a very slow expansion of the neoplastic cell clone.

The percentage of non-cycling blast cells in children with untreated acute lymphoblastic leukaemia (ALL) was investigated by staining smears for statin, a nuclear protein specifically present in non-growing resting cells. Results were compared with purified normal CD34-positive progenitors. A low fraction of ALL and CD34-positive cells expressed statin (2.9 +/- 3.8% and 2.8 +/- 3.1%, respectively), the growth fraction assessed by staining for the nucleolar antigen p120 was 94% in both ALL and CD34-positive cell samples. From this analysis it can be concluded that the compartment of non-replicating cells in ALL as well as in normal CD34-positive precursor cells collected from peripheral blood is very small and that most cells are cycling.