| First Author | Honda H | Year | 2001 |
| Journal | Blood Cells Mol Dis | Volume | 27 |
| Issue | 1 | Pages | 265-78 |
| PubMed ID | 11358387 | Mgi Jnum | J:69190 |
| Mgi Id | MGI:1934278 | Doi | 10.1006/bcmd.2000.0374 |
| Citation | Honda H, et al. (2001) Model mice for bcr/abl-positive leukemias. Blood Cells Mol Dis 27(1):265-78 |
| abstractText | ABSTRACT p210(bcr/abl) is detected in almost all chronic myelogenous leukemia (CML) patients and a significant number of acute lymphoblastic leukemia (ALL) cases. It is generated by a reciprocal chromosomal translocation, t(9;22) (q34;q11), and the enhanced kinase activity of the protein is believed to be implicated in the pathogenesis of the diseases. To examine its oncogenicity in vivo and to create an animal model for BCR/ABL-positive leukemias, we generated transgenic mice expressing p210(bcr/abl) driven by the promoter of the mouse tec gene, a cytoplasmic tyrosine kinase preferentially expressed in early hematopoietic progenitors. While the founder mice showed excessive proliferation of lymphoblasts shortly after birth and were diagnosed as ALL, the transgenic progeny reproducibly exhibited marked granulocyte hyperplasia with thrombocytosis after a long latent period, which closely resembles the clinical course of human CML. In addition, to investigate whether loss of p53 would play a role in the transition from chronic phase to blast crisis of CML, we crossmated p210(bcr/abl) transgenic (BCR/ABL(tg/-)) mice with p53 heterozygous (p53(+/-)) mice and generated p210(bcr/abl) transgenic, p53 heterozygous (BCR/ABL(tg/-) p53(+/-)) mice, in which a somatic alteration in the residual p53 allele directly abrogates p53 function. The BCR/ABL(tg/-) p53(+/-) mice exhibited rapid proliferation of blast cells and died in a short period compared with their wild-type (BCR/ABL(-/-) p53(+/+)), p53 heterozygous (BCR/ABL(-/-) p53(+/-)), and p210(bcr/abl) transgenic (BCR/ABL(tg/-) p53(+/+)) littermates. Interestingly, the normal p53 allele was frequently and preferentially lost in the tumor tissues, providing in vivo evidence that acquired loss of p53 contributes to the blastic transformation of p210(bcr/abl)-expressing hematopoietic cells. Our transgenic mice will be a useful model for investigating oncogenic properties of p210(bcr/abl) in vivo and will provide insights into the molecular mechanism(s) underlying the progression from chronic phase to blast crisis of CML. Copyright 2001 Academic Press. |
