title: Gene expression profile of protein kinases reveals a distinctive signature in chronic lymphocytic leukemia and in vitro experiments support a role of second generation protein kinase inhibitors.
abstract: To investigate the role of protein kinases (PKs) in chronic lymphocytic leukemia (CLL), we performed gene expression profile on 505 PK genes. Comparison between CLL with acute lymphocytic leukemia (ALL) patients highlighted an homogeneous up-modulation of several PKs in CLL, 16 also overexpressed in two additional CLL cohorts. Q-PCR analysis confirmed these findings. No differences were observed in the main prognostic subclasses, indicating that PK overexpression is specific of the disease itself. Tests in vitro showed that Dasatinib partially reduced CLL cells viability, mostly in IGHV germline patients. These findings suggest that treatment with second generation tyrosine kinase (TK) inhibitors may represent an attractive therapeutic strategy for CLL patients.
authors.affiliation: Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Monica
authors.initials: M
authors.lastname: Messina
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Simona
authors.initials: S
authors.lastname: Santangelo
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000145:classification / Q000627:therapeutic use; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000145:classification* / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase