In vitro evaluation of multiple kinetic parameters in human leukemia by quantitative 14-C autoradiography
Ucci, G.; Riccardi, A.; Danova, M.; Montecucco, C.M.; Ascari, E.
Haematologica 70(2): 101-105
1985
ISSN/ISBN: 0390-6078 PMID: 3924770 Document Number: 256398
DNA synthesis time (Ts, evaluated by quantitative 14-C autoradiography), 3H-thymidine labeling index (Li) and growth fraction (GF, evaluated by a morphological method devised by Gavosto et al.), were studied for bone marrow cells from two patients with normal appearing myelopoiesis and 10 patients with leukemia; 1 with Ph1 positive chronic myeloid leukemia (CML), 6 with acute non lymphoblastic and 3 with acute lymphoblastic leukemias (AnLL and ALL) at different stages of disease. Using a simple model of steady state growth, other kinetic parameters were calculated from those experimentally determined (cell cycle time, Tc; relative production rate, PR; compartment residence time, CRT). The values for the differencs kinetic parameters, either experimentally determined or calculated, overlap those reported by other investigators and those obtained by in vivo injection of radiolabels. The Ts values of bone marrow blasts in acute leukemia ranged from 10 to 34 hours; estimates of the other parameters (Li from 3.3 to 17.0%, GF from 12.7 to 50.4%, Tc from 31.8 to 290 hrs, PR from 1 to 4 cells/1000/hr) indicate a pattern of slow proliferation when the disease becomes clinically evident. In CML, the Ts appears normal for all myeloid precursors (11.5 hrs for myeloblasts, 11.7 promyelocytes and 16.1 hrs from myelocytes), but the kinetic patterns shows delay at all maturation levels, suggesting increased input from the stem cell pool rather than increased rate of proliferation of the recognizable myeloid precursors. We conclude that our approach to the study of cell kinetics in man in vitro methods is feasible in that it gives results which are in good agreement with those reported by in vivo injection of radiolabels.