Acute Promyelocytic Leukemia: A View from a Mouse

Murine models of human neoplasms are being used to expand our understanding of pathogenesis and to develop improved cancer therapies. MRP8-PMLRARα transgenic mice represent one model of human acute promyelocytic leukemia (APL). These mice develop leukemias that mirror characteristic features of human APL including responsiveness to retinoic acid and arsenic. This model is proving its value in elucidating mechanisms by which PMLRARα contributes to leukemia, identifying genetic changes that cooperate to cause leukemia, and investigating new molecular targets for leukemia therapy. These studies suggest that acute myeloid leukemias (AMLs) such as APL result from genetic changes that combine to both impair differentiation and allow immature cells to survive and proliferate outside of a normal microenvironment. Retinoic acid targets the central molecular lesion in human APL and has greatly improved survival. Molecularly targeted therapies that either restore maturation or abrogate growth autonomy represent a hope for improving survival of patients with other subtypes of AML.