Studies of Cellular Proliferation in Human Leukemia. I. Estimation of Growth Rates of Leukemic and Normal Hematopoietic Cells in Two Adults with Acute Leukemia Given Single Injections of Tritiated Thymidine

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Abstract

Two adults with rapidly progressive acute myeloblastic and myelomonoblastic leukemia were given single injections of tritiated thymidine, and measurements were made of the growth rates of their leukemic and normal hematopoietic cells by radioautographic methods. Although almost all leukemic blasts in both marrow and blood were metabolically active as shown by their ability to incorporate tritiated uridine and leucine in vitro, only 5.6% and 6.1% of the blasts in the marrow and even fewer in the blood incorporated tritiated thymidine. The mitotic indexes of the marrow blasts were 0.66% and 0.52%; no circulating blasts were dividing. The mean generation times of the actively proliferating blasts were estimated to be 49 and 83 hours. This cannot be equated with the doubling time of the total leukemic population as there is evidence that many blasts fail to continue dividing and die. The mean durations of the phases of the blasts' mitotic cycles were as follows: DNA synthesis (S) = 22 and 19 hours, premitosis (G2) = 3 hours, mitosis (M) = 0.47 and 0.62 hour (minimal estimates), and postmitosis (G1) = 24 and 61 hours. In both patients the maximal mean transit time of the blasts in the blood was 36 hours, and the minimal numbers of actively dividing blasts present were 1.6 and 2.6 × 109 per kg of body weight.

Authors

Bayard Clarkson, Takeshi Ohkita, Kazuo Ota, Jerrold Fried