The Size and Transit Time of Nondividing Subpool of Precursor Cells in Acute Leukemia

1. In order to elucidate the postulation and to quantitate the size and transit time of the nondividing subpool of precursor cells in acute leukemia, mathematical formulas based on a prolonged-labeling model were derived for the following kinetic parameters: (1) DNA synthesis time and generation time of dividing precursor cells in normal hemopoiesis and in acute leukemia. (2) size and transit time of the nondividing subpool of precursor cells in acute leukemia. The validity of the assumptions made in the model was discussed.

2. In vitro experimental estimation of the above kinetic parameters was done for the myeloid precursor pool in four cases: two with normal hemopoiesis; one, acute myeloid leukemia; one, subacute myeloid leukemia.

3. Variable decrease with time in availability of tritiated thymidine given initially in single dose to the in vitro system was observed and discussed.

4. DNA synthesis time and generation time of the dividing myeloid precursor cells in the two leukemic patients were not significantly different from, and were no shorter than, the corresponding values for normal myeloid precursor cells in the two nonleukemic patients. Thus it allows the prediction that as much as 86 per cent of the myeloid precursor cells in the marrow may be nondividing in acute myeloid leukemia.

5. In a case of acute myeloid leukemia about 87 per cent of the myeloid precursor cells in the marrow were estimated as nondividing with nondividing subpool transit time of about 32 days in closed in vitro system. The probable meanings of these in vitro estimates in vivo were discussed.

6. The result and analytical review of literature support the postulation of heterogeneous acute leukemia precursor cells with the nondividing fraction consisting of end cells being maintained by the dividing fraction. It is also suggested that a small fraction of nondividing cells may be capable of DNA synthesis and thus be initially-labeling. More definitive approaches to the problems await future investigation.