We have derived several strains of transgenic mice that use mutant or wild-type versions of the immunoglobulin heavy chain enhancer to over- express the myc oncogene. Normally, the heavy chain enhancer functions only in B cells; however, the mutations relieve constitutive suppression of the enhancer and allow it to activate myc gene expression in non-B cells as well as B cells. The strains with wild-type enhancer constructs invariably succumb to pre-B or mature B cell lymphomas while the transgenic mice with the mutant enhancers get tumors encompassing a wider spectrum of hematopoietic differentiation including pro-B, pre-T, T, and macrophage tumors in addition to pre-B and B cell tumors. Extensive phenotypic and molecular characterization of over 100 early B- lineage tumors has allowed us to characterize 4 stages of pro-B and pre- B cell differentiation and to show their precursor-product relationships along the B cell differentiation pathway.
