Nilotinib interferes with cell cycle, ABC transporters and JAK-STAT signaling pathway in CD34+/lin- cells of patients with chronic phase chronic myeloid leukemia after 12 months of treatment

• Published in: PloS one Vol. 14; no. 7; p. e0218444
• Main Authors: Trojani, Alessandra, Pungolino, Ester, Dal Molin, Alessandra, Lodola, Milena, Rossi, Giuseppe, D’Adda, Mariella, Perego, Alessandra, Elena, Chiara, Turrini, Mauro, Borin, Lorenza, Bucelli, Cristina, Malato, Simona, Carraro, Maria Cristina, Spina, Francesco, Latargia, Maria Luisa, Artale, Salvatore, Spedini, Pierangelo, Anghilieri, Michela, Di Camillo, Barbara, Baruzzo, Giacomo, De Canal, Gabriella, Iurlo, Alessandra, Morra, Enrica, Cairoli, Roberto
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2019; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; ABC transporters; AKT protein; Antineoplastic agents; ATP-Binding Cassette Transporters - blood; Biochemistry; Biology and Life Sciences; Bone marrow; Cancer therapies; CD34 antigen; Cell cycle; Cell Cycle - drug effects; Cell differentiation; Cell growth; Cell proliferation; Cellular signal transduction; Chromosome replication; Chromosomes; Chronic myeloid leukemia; Clustering; Complications and side effects; Criminal investigation; Deoxyribonucleic acid; Deregulation; Diagnosis; Disease; DNA; DNA biosynthesis; DNA damage; DNA microarrays; DNA probes; DNA replication; Dosage and administration; Drug resistance; Drug therapy; Enzyme inhibitors; Female; Gene expression; Gene Expression Regulation, Leukemic - drug effects; Genes; Genetic aspects; Genomes; Hematology; Hospitals; Humans; Inhibitor drugs; Interleukin 7; Internal medicine; Janus kinase 2; Janus Kinases - blood; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Male; MAP kinase; Medicine and Health Sciences; Middle Aged; Myeloid leukemia; Neoplasm Proteins - blood; Nilotinib; Phenols (Class of compounds); Phenotypes; Physiological aspects; Protein-tyrosine kinase; Proteins; Pyrimidines - administration & dosage; Replication; Research and analysis methods; Ruxolitinib; Signal transduction; Signal Transduction - drug effects; Signaling; STAT Transcription Factors - blood; Stem cells; Targeted cancer therapy; Time Factors; Tyrosine; Italy

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyro...