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Effects on Leukemic Clonogenic Cells in Murine Myeloid Leukemia of 1-ß-D-Arabinofuranosylcytosine and the Anthracyclines Adriamycin, Daunomycin, Aclacinomycin A, and 4'-Epidoxorubicin¹

First Department of Internal Medicine, Tokyo Medical and Dental University, 5-45, Yushima 1-Chome, Bunkyo-ku, Tokyo 113 [N. N., Y. Y., I. M., S. T., N. A.], and Division of Radiation Health, National Institute of Radiological Sciences, Anagawa 4-Chome, Chiba-shi, Chiba-ken 260 [Y. I.], Japan

M-3 murine myeloid leukemic cells undergo terminal divisions making colonies in methylcellulose culture and also renew themselves in methylcellulose and suspension; leukemic clonogenic cells are characteristic as stem cells. The effects of 1-ß-D-arabinofuranosylcytosine and four anthracyclines (Adriamycin, daunomycin, aclacinomycin A, and 4'-epidoxorubicin) on M-3 leukemic clonogenic cells were studied. 1-ß-D-Arabinofuranosylcytosine was effective in reducing primary and secondary colonies in methylcellulose and the growth of clonogenic cells in suspension. In contrast, the anthracyclines were not so effective in reducing secondary colonies in methylcellulose or clonogenic cells in suspension as to suppress primary colonies in methylcellulose. The results suggest that 1-ß-D-arabinofuranosylcytosine but not the anthracyclines is effective for not only terminal divisions but also self-renewal of leukemic clonogenic cells. The study will be used as a practical screening test to examine the effects of antitumor agents on leukemic blast progenitors.

¹ Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, and the Uehara Memorial Foundation, Japan.

² To whom requests for reprints should be addressed, at First Department of Internal Medicine, tokyo Medical and Dental University, 5-45, Yushima 1-Chome, Bunkyo-ku, Tokyo 113, Japan.

Received 10/10/86. Revised 1/20/87. Accepted 2/ 9/87.