E2A-PBX1, THE T(1, 19) TRANSLOCATION PROTEIN OF HUMAN PRE-B-CELL ACUTE LYMPHOCYTIC-LEUKEMIA, CAUSES ACUTE MYELOID-LEUKEMIA IN MICE

被引:144
作者
KAMPS, MP
BALTIMORE, D
机构
[1] Department of Pathology, School of Medicine, University of California, San Diego, CA 92093
关键词
D O I
10.1128/MCB.13.1.351
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
One-quarter of pediatric pre-B-cell leukemias contain the t(1;19) chromosomal translocation, which fuses 5' exons encoding the transactivation domain of the E2A transcription factor gene to 3' exons encoding the putative DNA-binding region of the unusual homeobox gene, PBX1. To test the leukemic potential of this fused gene, a cDNA encoding its major protein product, p85E2A-Pbx1, was incorporated into a retrovirus construct and introduced into normal mouse marrow progenitors by infection. The cells were used in a bone marrow transplantation protocol to reconstitute the hematopoietic compartments of lethally irradiated recipients. After 3 to 8 months, reconstituted mice developed acute myeloid leukemias that expressed high levels of p85E2A-Pbx1 and were readily transmissible to immunocompetent mice. Most acute myeloid leukemias also grew as granulocytic sarcomas and exhibited some neutrophilic differentiation. These results demonstrate a causative role for p85E2A-Pbx1 in human acute leukemia and indicate that the oncogenic potential of Pbx1 is not limited to pre-B-cell malignancies.
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页码:351 / 357
页数:7
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