The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML)

The blast cell population in AML includes progenitors capable of colony formation in culture. Certain properties of these progenitors have been determined, including their capacity for self-renewal and their sensitivities to the chemotherapeutic drugs cytosine arabinoside (Ara- C) and adriamycin (Adria). Wide patient to patient variation was found in these properties, although they were stable during the course of the disease in each patient. We tested the properties, together with clinical risk factors, as attributes contributing to the variation in remission induction and survival. As univariate parameters, self- renewal and Ara-C sensitivity contributed to remission induction, but only self-renewal was related to survival. In multivariate analysis, self-renewal, age and percentage blasts in the marrow contributed to outcome variation; drug sensitivities were not significant. We conclude that self-renewal, a biological property of malignant AML clones, although measured in culture, plays a significant role in determining response to treatment and survival in AML.