Osteopontin is upregulated by BCR-ABL.
Chronic myelogenous leukemia (CML) is characterized by its hallmark oncogene BCR-ABL and the progression from a chronic phase toward an acute leukemia, with a differentiation arrest of the leukemic clone. In the present study, we conducted a microarray analysis using an inducible model of BCR-ABL expression based on the TET-OFF system, and we found that osteopontin (OPN), a component of stem cell niche, is overexpressed in BCR-ABL-expressing cells. Studies using mutant forms of BCR-ABL demonstrated that the BCR-ABL-induced OPN overexpression was a tyrosine kinase-dependent event. Furthermore, OPN concentration was significantly increased in the serum of leukemic mice generated by transplantation of BCR-ABL-expressing bone marrow cells. Most importantly, a significant increase of OPN concentration was observed in the serum of CML patients as compared to controls. Overall these results show that OPN is deregulated by BCR-ABL oncogene and suggest that OPN could be involved in CML stem cell biology.
INSERM U362, Institut Gustave-Roussy, Villejuif, France.
S
S
Flamant
T
T
Kortulewski
A
A
Dugray
M-L
ML
Bonnet
M
M
Guillier
F
F
Guilhot
J-H
JH
Bourhis
W
W
Vainchenker
D
D
Tronik-Le Roux
A G
AG
Turhan
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D051379:Mice; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000378:metabolism*; D015854:Up-Regulation
C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D016044:Fusion Proteins, bcr-abl