Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice.
Lethally irradiated mice reconstituted with bone marrow expressing P210 BCR-ABL can develop myeloproliferative syndromes that resemble the initial phase of human chronic myelogenous leukemia (CML). Mice that develop the CML-like syndrome can be segregated into two groups based on the latency with which the granulocytic disease appears--early onset (< 20 weeks) and late onset (> 20 weeks). Only cells from mice exhibiting the late-onset CML-like syndrome can efficiently propagate the disease when transplanted into sublethally irradiated syngeneic recipients. Mice engrafted with late-onset murine CML cells develop a range of hematopoietic disorders that originate from multipotent stem cells. The chronic granulocytic hyperplasia can be propagated by serial transplantation into secondary and tertiary recipient mice. The majority of transplanted mice succumb to acute myeloid and B- and T-lymphoid leukemias. These data support the idea that late-onset murine CML originates from a multipotent progenitor cell with a high replicating capacity. The inability to transplant the disease from mice developing the early-onset CML-like syndrome suggests that this disorder may originate from more differentiated progenitor cells with limited replication capacity that have undergone clonal expansion but are not immortalized. Although both early- and late-onset CML-like syndromes exhibit granulocytic hyperplasia, these disorders represent distinct diseases that appear to originate from different hematopoietic cell types. The late-onset CML-like disease and transfer to secondary recipients provides a useful murine model with features of the chronic and acute phases of human CML.
Gishizky
M L
ML
Howard Hughes Medical Institute, University of California, Los Angeles 90024.
Johnson-White
J
J
Witte
O N
ON
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D016313:Genes, abl; D006402:Hematologic Diseases / Q000235:genetics* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009857:Oncogenes; D010641:Phenotype
D004247:DNA; D016044:Fusion Proteins, bcr-abl