Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitro.
Expression of the bcr-abl oncogene in multipotent progenitor cells (MPPCs) is implicated as a key event in the development of chronic myelogenous leukemia. Bone marrow enriched for MPPCs was infected with a retrovirus that carried bcr-abl. The mixed-lineage colonies that resulted were responsive to growth factors and could differentiate. These cells later became growth factor-independent but, when injected into severe combined immunodeficient mice, were not leukemogenic. Thus, the presence of bcr-abl alone does not cause growth factor independence, although it initiates a stepwise process. This system may prove useful in the study of other oncogenes that cause leukemia.
Gishizky
M L
ML
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
Witte
O N
ON
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D004352:Drug Resistance, Microbial / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D019089:Stem Cell Factor; D014162:Transfection
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D016044:Fusion Proteins, bcr-abl; D005472:Fluorouracil