THE PROCESS OF LEUKEMOGENESIS

Leukemias are monoclonal diseases that arise from cells in the hematop oietic stem and progenitor cell compartment. Consistent with emerging models of carcinogenesis, leukemogenesis is an evolutionary process th at involves multiple independent genetic and epigenetic events. Over t he last half-century a predominant paradigm has emerged to describe le ukemia developing secondary to alkylating drug therapy or exposure to benzene in which progressive dysplastic changes, accompanied by a dist inct pattern of clonal cytogenetic abnormalities, give rise to acute m yelogenous leukemia. Characterization of these clonal chromosomal aber rations, together with observed alterations in other growth-promoting genes, provides a useful framework for studying chemical leukemogenesi s and for use in understanding the origins and development of leukemia in general.