Ph-positive leukemia: a transgenic mouse model.
The presence of the BCR/ABL chimeric gene is the hallmark of defined types of human leukemia. To increase our knowledge of the oncogenic processes and to develop a model for this type of leukemia we generated a BCR/ABL (P190) transgenic mouse line. Over 95% of mice of this line die of leukemia or leukemia/lymphoma within 35-200 days of age. Karyotypically visible genetic alterations were absent from the early stages of BCR/ABL generated leukemia. A high frequency of aneuploidy was found in advanced leukemia indicating a primary and pivotal role for BCR/ABL in leukemogenesis. Moreover, the data suggest that BCR/ABL has a destabilizing effect on the regulation of the cell cycle. BCR/ABL expression was also found in tissues other than hematopoietic cells. However, this did not result in the development of solid tumors, strongly suggesting that the oncogenicity of BCR/ABL is limited to the hematopoietic lineage.
Groffen
J
J
Department of Pathology, Children's Hospital of Los Angeles, CA 90027.
Voncken
J W
JW
Kaartinen
V
V
Morris
C
C
Heisterkamp
N
N
D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic
D016044:Fusion Proteins, bcr-abl