Imatinib restores expression of CD62L in BCR-ABL-positive cells.
Chronic myelogenous leukemia (CML) is characterized by aberrant trafficking of malignant hematopoietic progenitor cells in the peripheral blood. Expression of the cell adhesion molecule CD62L was reported to be significantly lower in CML patients than in normal controls. We studied whether the transcription of CD62L in CML cells is dependent on the activity of the BCR-ABL tyrosine kinase. Following addition of the Abelson (ABL) tyrosine kinase inhibitor imatinib (formerly STI571) to two BCR-ABL-positive cell lines (BV173, SD-1), we observed a dose-dependent increase in CD62L RNA levels of up to 45-fold by a quantitative, real-time polymerase chain reaction and an increase in the amount of cell surface-bound CD62L of up to 18-fold by quantitative flow cytometry, respectively. These data are validated by an increased CD62L expression in the bone marrow of patients (n=6) with advanced CML who received imatinib. Restoration of defective cell adhesion mediated via the CD62L pathway may be one mechanism of action of imatinib in BCR-ABL-positive leukemias.
Fruehauf
S
S
Department of Internal Medicine V, University of Heidelberg, Germany. stefan_fruehauf@med.uni-heidelberg.de
Topaly
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J
Schad
M
M
Paschka
P
P
Gschaidmeier
H
H
Zeller
W J
WJ
Hochhaus
A
A
Ho
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D019041:L-Selectin / Q000096:biosynthesis* / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019041:L-Selectin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl