title: Evaluation of CML model cell lines and imatinib mesylate response: determinants of signaling profiles.
abstract: Our understanding of the mechanisms by which BCR-ABL drives CML is based, in part, on the use of model cell lines such as the K562 cell line. However, the BCR-ABL translocation may occur via a number of different junction points. In addition, CML is a disease of hematopoietic stem cells and, as a result, can give rise to multiple lineages of tumor cells. In this study, we examined the cellular signaling profiles following imatinib mesylate treatment of eight model CML and ALL cell lines that encompass three BCR-ABL junction points and multiple lineages. We used phosphorylation-specific antibodies and flow cytometry to determine the kinase and pathway activation states with each of the cell lines before and after imatinib mesylate exposure. The comparisons of signaling response profiles, junction points and lineages indicate that cell line lineage rather than BCR-ABL junction point may determine cellular response to imatinib mesylate. The large amount of variation observed among the cell lines suggests that further analysis is required to understand the complex signaling profiles present in CML patients.
authors.affiliation: Cell Signaling Technology, 166B Cummings Center, Beverly, MA 01915, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Wetzel
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Goss
authors.forename: Brett
authors.initials: B
authors.lastname: Norris
authors.forename: Lana
authors.initials: L
authors.lastname: Popova
authors.forename: Michael
authors.initials: M
authors.lastname: Melnick
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Smith
mesh_terms: D000818:Animals; D001549:Benzamides; D045744:Cell Line, Tumor; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D001549:Benzamides; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl