A hypothesis regarding the development of acute myeloid leukemia from preleukemic disorders. The role of protooncogenes.

Acute nonlymphocytic leukemia is often preceded by a preleukemic phase that can be characterized by a reduction in hematopoiesis, by ineffective hematopoiesis, or by a myeloproliferative/myelodysplastic state. The time between onset of the preleukemic state and the appearance of leukemia is quite variable, and at times such evolution does not occur. These clinical observations are compatible with the multistep hypothesis of tumor development. In studies underway in our laboratory, chronic myelogenous leukemia (CML) is being used as a model system to study the steps in and possible mechanisms underlying the development of preleukemia and its evolution to acute leukemia. Chronic myelogenous leukemia is particularly suited for this role because the chronic phase of the disease is an easily identifiable myeloproliferative state that invariably evolves into acute leukemia. In the discussion that follows, this clinical entity is used to develop a general model for the preleukemias and their evolution to acute leukemia.