Molecular mechanisms underlying normal growth and differentiation are altered in cancer. Activation of growth-promoting genes and inactivation of differentiation and growth-arrest genes represent important steps in the evolution of a malignant clone. Normal blood cell formation and leukemia offer attractive systems for understanding malignant transformation because of the well-defined stages of blood cell maturation, the distinct subsets found in normal circulation and the recurrent chromosomal alterations in leukemia. The clinical outcome of leukemic patients is tightly correlated with chromosomal abnormalities. Our goal is to establish how the normal pathways of hematopoietic growth arrest and differentiation are perturbed during malignant transformation.