E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice.

摘要: One-quarter of pediatric pre-B-cell leukemias contain the t(1;19) chromosomal translocation, which fuses 5' exons encoding transactivation domain E2A transcription factor gene to 3' ecoding putative DNA-binding region unusual homeobox gene, PBX1. To test leukemic potential this fused a cDNA its major protein product, p85E2A-Pbx1, was incorporated into retrovirus construct and introduced normal mouse marrow progenitors by infection. The cells were used in bone transplantation protocol reconstitute hematopoietic compartments lethally irradiated recipients. After 3 8 months, reconstituted mice developed acute myeloid that expressed high levels p85E2A-Pbx1 readily transmissible immunocompetent mice. Most also grew as granulocytic sarcomas exhibited some neutrophilic differentiation. These results demonstrate causative role for human leukemia indicate oncogenic Pbx1 is not limited malignancies.