Protein kinase gene expression profiling and in vitro functional experiments identify novel potential therapeutic targets in adult acute lymphoblastic leukemia.
BACKGROUND
Despite recent improvements in the treatment of acute lymphoblastic leukemia (ALL), adult patients still have an overall poor outcome. The future of ALL management relies on the introduction of novel targeted therapies. The authors sought to assess if protein kinases (PKs), frequently deregulated in cancer, show an altered expression pattern and can be considered as suitable therapeutic targets in adult ALL.


METHODS
The authors studied the PK gene expression profile by oligonucleotide arrays in 133 adult ALL samples at the onset of the disease and subsequently performed in vitro experiments to evaluate the sensitivity to first- and second-generation PK inhibitors of a set of ALL cell lines, as well as of primary ALL cells.


RESULTS
The study documents a distinctive PK signature for different adult ALL subgroups; the PKs identified include several tyrosine kinase (TK) genes, especially in E2A/PBX+ B-lineage ALL (B-ALL), B-ALL without known molecular abnormalities, and T-lineage ALL. Consistently, cell lines and primary samples belonging to these groups proved susceptible to TK inhibitors.


CONCLUSIONS
These results indicate that second-generation TK inhibitors may be effective in ALL subsets other than BCR/ABL+B-ALL and provide the rationale for testing the impact of the newly developed TK inhibitors in the management of adult ALL patients.
Messina
Monica
M
Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Chiaretti
Sabina
S
Tavolaro
Simona
S
Peragine
Nadia
N
Vitale
Antonella
A
Elia
Loredana
L
Sica
Simona
S
Levis
Alessandro
A
Guarini
Anna
A
Foà
Robin
R
D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics*
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases