Comparative proteomic analysis of chronic myelogenous leukemia cells: inside the mechanism of imatinib resistance.
Imatinib is the first molecular targeted therapy that has shown clinical success, but imatinib acquired resistance, although a rare event, is critical during the therapy of chronic myelogenous leukaemia (CML). With the aim of better understanding the molecular mechanisms accompanying acquisition of resistance to this drug, a comparative proteomic approach was undertaken on CML cell lines LAMA 84 S (imatinib sensitive) and LAMA 84 R (imatinib resistant). Forty-four differentially expressed proteins were identified and categorized into five main functional classes: (I) heat shock proteins and chaperones; (II) nucleic acid interacting proteins (binding/synthesis/stability); (III) structural proteins, (IV) cell signaling, and (V) metabolic enzymes. Several heat shock proteins known to complex Bcr-Abl were overexpressed in imatinib resistant cells, showing a possible involvement of these proteins in the mechanism of resistance. HnRNPs also resulted in being up-regulated in imatinib resistant cells. These proteins have been shown to be strongly and directly related to Bcr-Abl activity. To our knowledge, this is the first direct proteomic comparison of imatinib sensitive/resistant CML cell lines.
Ferrari
Germano
G
University of Florence, AUO Careggi, Department of Hematology, Florence, Italy.
Pastorelli
Roberta
R
Buchi
Francesca
F
Spinelli
Elena
E
Gozzini
Antonella
A
Bosi
Alberto
A
Santini
Valeria
V
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D008954:Models, Biological; D010879:Piperazines / Q000627:therapeutic use*; D040901:Proteomics / Q000379:methods*; D011743:Pyrimidines / Q000627:therapeutic use*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate