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Cytotoxicity of 4-Hydroperoxycyclophosphamide for the Blast Progenitors of Acute Myeloblastic Leukemia¹

First Department of Internal Medicine, Tokyo Medical and Dental University, 5-45, Yushima 1-Chome, Bunkyo-ku, Tokyo 113, Japan

The effects of 4-hydroperoxycyclophosphamide (4-HC), an analogue of cyclophosphamide, on the blast progenitors from eight acute myeloblastic leukemia patients were studied in methylcellulose and suspension cultures. Leukemic blast progenitors undergo terminal divisions in methylcellulose culture, making blast colonies. Cells in primary colonies can make secondary colonies after replating in fresh methylcellulose medium. Leukemic blast progenitors grow exponentially in suspension culture for periods of weeks. The ability to form secondary colonies and the exponential growth in suspension culture are considered to reflect the self-renewal of blast progenitors. 4-HC suppressed primary blast colonies in a dose-responsive manner. Secondary colonies were not significantly affected by 4-HC. Although the clonogenic cell recovery was suppressed by 4-HC, leukemic blast progenitors were less sensitive to 4-HC in suspension culture than in methylcellulose culture. The results suggest that 4-HC is effective in suppressing the terminal divisions of blast progenitors but not as effective against the self-renewal of 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.

Received 8/13/87. Revised 12/29/87. Accepted 1/19/88.