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

Simona Tavolaro; Sabina Chiaretti; Monica Messina; Nadia Peragine; Ilaria Del Giudice; Marilisa Marinelli; Simona Santangelo; Francesca Romana Mauro; Anna Guarini; Robin Foà

doi:10.1016/j.leukres.2009.11.005

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

Leuk Res. 2010 Jun;34(6):733-41. doi: 10.1016/j.leukres.2009.11.005. Epub 2009 Dec 24.

Authors

Simona Tavolaro¹, Sabina Chiaretti, Monica Messina, Nadia Peragine, Ilaria Del Giudice, Marilisa Marinelli, Simona Santangelo, Francesca Romana Mauro, Anna Guarini, Robin Foà

Affiliation

¹ Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento, Rome, Italy.

PMID: 20036005
DOI: 10.1016/j.leukres.2009.11.005

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.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Adult
Aged
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / classification
Antineoplastic Agents / therapeutic use
Cluster Analysis
Female
Gene Expression Profiling
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Leukemic
Hematologic Neoplasms / genetics
Hematologic Neoplasms / metabolism
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Phosphorylation / genetics
Phosphorylation / physiology
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / classification*
Protein Kinase Inhibitors / therapeutic use*
Protein Kinases / genetics*
Protein Kinases / metabolism
Tumor Cells, Cultured
ZAP-70 Protein-Tyrosine Kinase / genetics

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Protein Kinases
ZAP-70 Protein-Tyrosine Kinase