The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr-Abl activity in chronic myeloid leukemia.
We have identified differentially regulated genes in chronic myeloid leukemia (CML) cells upon short treatment with the broad-spectrum Bcr-Abl inhibitor dasatinib. The highly specific Bcr-Abl inhibitor nilotinib caused a very similar gene expression signature, validating the identified differentially regulated genes as a read-out of Bcr-Abl activity and implying that Bcr-Abl is the functionally central target of dasatinib in CML cells. Among the strongest downregulated genes, we have further validated the activation marker CD69 and the chemokine interleukin (IL)-8. Expression of both proteins is upregulated upon Bcr-Abl expression and inhibited by dasatinib and nilotinib. IL-8 may thus be a useful marker for the monitoring of CML inhibitor efficacy and play a potential pathophysiological role in CML.
Hantschel
Oliver
O
Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria.
Gstoettenbauer
Agnes
A
Colinge
Jacques
J
Kaupe
Ines
I
Bilban
Martin
M
Burkard
Thomas R
TR
Valent
Peter
P
Superti-Furga
Giulio
G
D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D000069439:Dasatinib; D015536:Down-Regulation / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods*; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016209:Interleukin-8 / Q000032:analysis* / Q000235:genetics; D037181:Lectins, C-Type; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy; D011743:Pyrimidines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D000069439:Dasatinib; D016044:Fusion Proteins, bcr-abl; D016209:Interleukin-8; D037181:Lectins, C-Type; D011743:Pyrimidines; D013844:Thiazoles; D000099192:CD69 Antigens; C498826:nilotinib