Molecular genetics of human leukemia.

Human leukemias are clonal hemopathies generally characterized by acquired somatic mutations, including translocations, deletions, and insertions. Ten years ago, the first leukemia-related chromosomal translocation, the Philadelphia chromosome, was cloned and fully characterized at the molecular level. Since then, a plethora of chromosomal translocations and mutations has been associated with leukemogenesis. Analysis and comparison of this bewildering array of genetic changes have helped identify shared paradigms and themes in the mechanisms of transformation of hematopoietic cells. This information will guide the development of improved therapies that take into account the cytogenetic and molecular characteristics of human leukemias. This review summarizes the current knowledge of the nature of the genetic changes associated with leukemogenesis and discusses their consequences at the molecular and cellular levels.