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Biomarkers for Diagnosis and Targeting of Resistance and Sensitivity to Imatinib Mesylate in Chronic Myelogenous Leukemia
Author(s) -
Goldknopf Ira L.,
Sheta Essam A.,
Talpaz Moshe,
Cortes Jorge,
Albitar Maher,
Kantarjian Hagop
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a499-c
Subject(s) - chronic myelogenous leukemia , imatinib mesylate , medicine , imatinib , leukemia , bone marrow , cancer research , myeloid leukemia
The ability to predict which patients are, or will become, resistant to a particular therapy is limited at present and would be a valuable asset in developing treatment strategies. To discover protein biomarkers that may predict cancer patients’ later response or resistance to imatinib mesylate (Gleevec®) and to provide clues to prevent or delay the onset of such resistance, bone marrow aspirate samples were taken from patients at time of diagnosis of Chronic Myelogenous Leukemia (CML). The patients were subsequently treated with imatinib and their response evaluated. The initial bone marrow aspirate samples were subjected to 2D gel electrophoresis, high sensitivity fluorescent staining, and quantitative digital image analysis. Of the >2500 spots resolved by this method, a group of 19 were found to be differentially expressed between responders and nonresponders, based upon significant and consistent differences in protein concentration of the spots. The spots were robotically excised, in‐gel trypsin digested, and subjected to identification by peptide mass fingerprint analysis. The protein identities, and their pattern of differential expression as a function of sensitivity or resistance to imatinib, suggest an integrated resistance mechanism and provide an indication of therapeutic targeting to overcome resistance to imatinib and other agents.