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Osteopontin is upregulated by BCR-ABL.
S Flamant1, T Kortulewski, A Dugray
1INSERM U362, Institut Gustave-Roussy, Villejuif, France.
Biochemical and Biophysical Research Communications
|July 5, 2005
Summary
Osteopontin (OPN) is overexpressed in chronic myelogenous leukemia (CML) due to the BCR-ABL oncogene. This study suggests OPN may play a role in CML stem cell biology.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chronic myelogenous leukemia (CML) is driven by the BCR-ABL oncogene.
- CML progresses from a chronic phase to acute leukemia with impaired leukemic cell differentiation.
- The role of stem cell niche components in CML pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of osteopontin (OPN) in BCR-ABL-mediated CML.
- To determine if OPN is deregulated by the BCR-ABL oncogene in CML.
Main Methods:
- Microarray analysis using an inducible TET-OFF model of BCR-ABL expression.
- Studies with mutant forms of BCR-ABL to assess tyrosine kinase dependence.
- Measurement of OPN serum concentrations in leukemic mice and CML patients.
Main Results:
- Osteopontin (OPN) was found to be overexpressed in BCR-ABL-expressing cells.
- BCR-ABL-induced OPN overexpression is dependent on tyrosine kinase activity.
- Significantly increased OPN serum concentrations were observed in CML patients and leukemic mice compared to controls.
Conclusions:
- Osteopontin (OPN) is deregulated by the BCR-ABL oncogene in CML.
- OPN may be involved in the biology of CML stem cells.
- OPN represents a potential biomarker or therapeutic target in CML.