Studies on Analogues of L-Cysteine and L-Cystine

Abstract

Selenium cystine was administered orally to 2 patients with acute leukemia and to 2 patients with chronic myeloid leukemia. In all patients there was a rapid decrease in the total leukocyte count as well as a decrease in spleen size. This effect was observed in patients refractory to other chemotherapeutic agents as well as in the usually resistant types of leukemia. In patients with chronic myeloid leukemia the immature granulocytes disappeared much more rapidly than the mature granulocytes. The most striking and consistent effects were observed in acute leukemia. One patient who had become resistant to 6-mercaptopurine appeared to reacquire sensitivity to this compound after receiving selenium cystine. These effects of selenium cystine on leukocytes correlate with the ability of selenium cystine to decrease the influx of S³⁵ L-cystine by leukemic leukocytes in vitro. Other potentially effective analogues of cystine (or cysteine) may therefore be selected by this technic. No changes were detected in any of the organs attributable to selenium cystine toxicity. The nausea and vomiting associated with the oral administration of selenium cystine was so severe that it was not possible to administer selenium cystine for a sufficient period of time to determine whether an appreciable remission can be obtained in leukemia. Further study is necessary to determine whether selenium cystine has any practical applicability in the chemotherapy of leukemia. Although the mechanism of action of selenium cystine is not known, these striking effects of an analogue of cystine on leukemia are further suggestive of the importance of cystine (cysteine) in the metabolism of leukocytes.