Modeling Chromosomal Translocations Using Conditional Alleles to Recapitulate Initiating Events in Human Leukemias

Consistent chromosomal translocations are associated with remarkable specificity in distinct tumor subtypes ( 1 ) and can be considered primary events in the initiation of the tumorigenic processes. They are present in more than 50% of all hematological malignancies and many have also been identified in mesenchymal (ie, sarcomas) tumors and some in epithelial tumors (eg, prostate cancer) ( 2 ). Since the first reciprocal translocations were reported in 1960 – 70s ( 1 – 4 ), abundant studies at cytogenetic and molecular level have been carried out to identify the involved genes. The cloning of the translocation breakpoints revealed that the main outcomes of the interchromosomal rearrangements are proto-oncogene activation by juxtaposition to T- or B-cell receptor genes or the creation of fusion genes encoding a chimeric oncogenic protein. The characterization of the chromosomal translocation products, in the acute cancers, showed that they tend to be transcription and developmental regulators, altering the transcription balance and the control of the fate of the affected cell, which led to the chromosomal translocation-master gene model ( 5 ).