Effects of 13-cis retinoic acid and Ara-C on differentiation and proliferation of non-promyelocytic acute myelogenous leukemia

An alternative to a cell-kill strategy for eradication of acute myelogenous leukemia, is to restore normal differentiation. Vitamin A derivatives demonstrate differentiation-inducing activity both in vitro and in vivo on promyelocytic leukemic cells. We tested the ability of 13-cis retinoic acid to reduce proliferation and induce differentiation in 10 samples from patients with acute non-promyelocytic leukemia. DNA synthesis and leukemia colony formation were affected to varying degrees by a prolonged exposure to the vitamin A compound. Morphologically and cytochemically no differentiation was determined either after 48 h in suspension cultures or 7 additional days in semi-solid cultures. Alkaline leukocyte phosphatase, a biochemical marker of differentiation, was significantly increased in five samples. DNA synthesis in these samples was significantly reduced as compared to samples failing to express alkaline leukocyte phosphatase following 13-cis retinoic acid treatment. DNA synthesis of these same 5 samples was also strongly inhibited by Ara-C. Expression of alkaline leukocyte phosphatase following 13-cis retinoic acid exposure may be a useful indicator for cells amenable to 13-cis retinoic acid or Ara-C treatment.