Aurora-A kinase expression in chronic lymphocytic leukemia

Aim and Hypothesis: Aurora kinases are serine/threonine kinases that are essential for regulating mitotic events such as centrosome maturation and segragation, mitotic spindle formation, control of spindle assembly checkpoint, chromosome segragation and cytokinesis. Aurora kinase A overexpression was associated with higher tumor grade, proliferation rate and poor prognosis in many solid organ tumors and haematological malignancies. The aim of this study is to determine the Aurora kinase A expression in patients with chronic lymphocytic leukemia. Method: Our prospective study was approved by the Ethics Committee of Adnan Menderes University. Newly diagnosed, untreated 41 CLL patients (22 males and 19 females with mean age of 70±10) and control group of 19 patients (7 males and 11 females with mean age of 53±20) with benign haematological diseases were included in this study. Bone marrow aspiration and biopsy was performed in all patients. Aurora kinase A mRNA expression could not be analyzed due to technical problem in only one patient of control group and this patient was excluded. Aurora kinase A expression was investigated using β-actin ve GAPDH housekeeping genes by quantitative RT-PCR (reverse transcriptase-polymerase chain reaction) method in bone marrow cells. Relative RNA level was performed via standard delta/delta Ct (δ/δ Ct). Aurora-A antibody was applied to all bone marrow biopsy sections of patients with CLL and control group for immunohistochemical analysis. 13q deletion, 17p deletion and trisomy 12 chromosomal abnormalities were investigated by FISH method in bone marrow aspirates of CLL patients. Statistical analysis of the differences between groups was assessed by Mann-Whitney-U, Chi-square and One-Way ANOVA tests in SPSS 15.0 Windows. A p-value of <0.05 was considered statistically significant. Results: There was no significant difference for Aurora kinase A mRNA expression between CLL patients and control group (p>0.05). Aurora kinase A immunohistochemical positivity in patients with CLL was statistically significant (p<0.001). Cytoplasmic and nuclear staining pattern was both seen in all Aurora kinase A positively stained CLL patients. There was no significant difference for immunohistochemical staining in CLL patients with chromosomal abnormalities 13q deletion, 17p deletion or trisomy 12 (p>0.05). Conclusion: Aurora kinase A mRNA overexpression was not detected in our study which has largest series of untreated patients with CLL. However, significant immunohistochemical staining represent that Aurora kinaz A might be a potential therapeutic target in CLL. Key Words: Aurora kinase A, chronic lymphocytic leukemia