Adenine analogs as potential differentiation therapy agents for acute myeloid leukemia

Although the frequency of complete remission in acute myeloid leukemia (AML) has increased, the median duration of such remission is only 9–15 months, even when remission is achieved by treatment with conventional cytotoxic antileukemic drugs. These results clearly call for improved therapies. AML is characterized by a differentiation block leading to the accumulation of immature cells. This maturation arrest can be reversed by certain agents. Several adenine analogs effectively induce the morphologic and functional differentiation of leukemia cells. Thus, adenine analogs, alone or in combination with other differentiation‐inducing agents, may be effective for the therapy of AML. However, the antileukemic analog that is the most suitable for the treatment of AML may depend on the leukemia subtype, since the sensitivity of leukemia cells to these analogs varied greatly among leukemia subtypes. The clinical usefulness of these adenine analogs is discussed. Drug Dev. Res. 59:14–22, 2003.