RADIOBIOLOGICAL FEATURES OF ACUTE MYELOBLASTIC-LEUKEMIA - COMPARISON OF SELF-RENEWAL VERSUS TERMINALLY DIFFERENTIATED POPULATIONS

Purpose: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radio sensitivity of the cells grown either in methylcellulose alone for 7 d ays, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells a nd suspension cultures have been developed because they allow self-ren ewal to occur: The exponential growth of the progenitors of AML cultur ed in suspension is due to self-renewal. Methods and Materials: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological , cytochemical, and immunophenotypic analysis, and by the use of growt h factors that did not stimulate the growth of T-lymphocytes. The cell -cycle distribution of the blasts was analyzed by flow cytometry and w as comparable for all samples. The irradiation was performed with gamm a-photons at a dose-rate of 0.05 Gy/min, similar to the clinical condi tions used in our institution for total body irradiation (TBI). Result s: The culture methods selected agressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radio sensitive than terminal dividing cells. In two cases, a shoulder was f ound in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e(-alpha D-beta D2)) With alpha/be ta values of 1.49 Gy and 3.12 Gy, respectively. Conclusion: The very l ow values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods t o determine the most appropriate technique for radiation ablation of b one marrow prior to bone marrow transplantation (BMT).