title: Label-free MSE proteomic analysis of chronic myeloid leukemia bone marrow plasma: disclosing new insights from therapy resistance.
abstract: Chronic myeloid leukemia (CML) is a pluripotent hematopoietic disorder that is currently considered incurable. The tyrosine kinase product of the Philadelphia chromosome, P210 BCR-ABL, provided a pathogenetic explanation for the initiation of the CML chronic phase and is the molecular therapeutic target for the disease. Imatinib mesylate, an orally available BCR-ABL kinase inhibitor, can induce haematologic and cytogenetic remission of CML. However, imatinib resistance occurs frequently, resulting in relapse. New treatment strategies are focusing on resistant CML stem cells and the bone marrow stroma. The identification of novel pathways and mechanisms in the bone marrow microenvironment could significantly contribute to the development of such strategies. In this work, we used a high-resolution label-free MS(E)  proteomic approach to identify differential protein expression in the CML bone marrow plasma of responsive and resistant patients. Oxidative lipid metabolism and regulation of the switch from canonical to noncanonical WNT signaling may contribute to CML resistance in the bone marrow compartment.
authors: Divisão de Laboratórios do CEMO, Instituto Nacional do Câncer, Rio de Janeiro, Brazil. pizzatti@inca.gov.br
authors: Luciana
authors: L
authors: Pizzatti
authors: Carolina
authors: C
authors: Panis
authors: Gabriela
authors: G
authors: Lemos
authors: Moisés
authors: M
authors: Rocha
authors: Rubens
authors: R
authors: Cecchini
authors: Gustavo H M F
authors: GH
authors: Souza
authors: Eliana
authors: E
authors: Abdelhay
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D011743:Pyrimidines / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020543:Proteome; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases