Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitro
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Updated: Jul 27, 2026
The MultiBac Protein Complex Production Platform at the EMBL
Published on: July 11, 2013
1Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
Abstract:
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.
Insights
The bcr-abl oncogene initiates chronic myelogenous leukemia development but doesn't solely cause growth factor independence in multipotent progenitor cells (MPPCs). Further steps are needed for leukemogenesis, suggesting a stepwise process.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chronic myelogenous leukemia (CML) development involves the bcr-abl oncogene.
- Multipotent progenitor cells (MPPCs) are crucial in CML pathogenesis.
Purpose of the Study:
- To investigate the role of bcr-abl oncogene in MPPCs.
- To understand the initial steps of CML development.
Main Methods:
- Bone marrow MPPCs were infected with a bcr-abl carrying retrovirus.
- Resulting colonies were analyzed for growth factor responsiveness and differentiation.
- Cells were injected into severe combined immunodeficient mice.
Main Results:
- Infected MPPCs formed mixed-lineage colonies responsive to growth factors and capable of differentiation.
- These cells acquired growth factor independence.
- However, they were not leukemogenic in immunodeficient mice.
Conclusions:
- bcr-abl oncogene expression alone is insufficient for causing growth factor independence.
- Leukemogenesis is a stepwise process initiated by bcr-abl.
- This model system can aid research on other leukemia-causing oncogenes.
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