Differentiation-Linked Leukemogenesis in Lymphocytes

Abstract

Most human lymphoid malignancies preserve a pattern of gene expression reflecting their proliferative activity and the development level of clonal expansion and maturation arrest. Characteristics of leukemia and other cancer cells frequently considered to reflect aberrant differentiation may more often reflect clonal selection of cell types that are normally infrequent and transitory. The differentiation status of progenitor or mature lymphoid cells influences which genetic elements are at risk of being exploited, via mutation, recombination, or deletion, for clonal advantage. These alterations may frequently arise spontaneously as a consequence of the unique developmental and functional programs of lymphoid cells and have as a major phenotypic consequence the stabilization of transitory cellular phenotypes.