期刊
MODERN PATHOLOGY
卷 21, 期 12, 页码 1428-1435出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2008.173
关键词
Aurora-A; CLL; chromatin; chromosomes; p53
类别
Aurora-A kinase is a cell-cycle-regulating kinase required for chromosomal segregation. Overexpression of Aurora-A kinase has been shown to correlate with tumor proliferation and chromosomal instability. We investigated Aurora-A kinase expression in peripheral blood and bone marrow of 47 chronic lymphocytic leukemia patients and 20 age-matched hematologically healthy subjects. Western blot analysis showed significantly higher Aurora-A levels in chronic lymphocytic leukemia (42 of 47) compared with lymphocytes of healthy subjects. However, Aurora-A mRNA expression in three chronic lymphocytic leukemia patients was similar to or lower than that of healthy control subjects. In 28 of 42 chronic lymphocytic leukemia patients with elevated Aurora-A kinase expression, one or more chromosomal abnormalities were detected, including trisomy 12 in 9 patients and deletion of the ataxia telangiectasia-mutated gene in 9 patients. Aurora-A was also detected in all (100%) chronic lymphocytic leukemia cases by immunohistochemistry, with a nuclear staining pattern. The larger prolymphocytes and paraimmunoblasts showed stronger Aurora-A kinase expression than did small lymphocytes. In contrast, normal bone marrow reactive lymphocytes were negative for Aurora-A with positive histiocytes and immature myeloid cells. Immunostaining for acetylated histone H3 showed a nuclear pattern in all 38 chronic lymphocytic leukemia cases and double labeling showed coexpression of acetylated histone H3 and Aurora-A. In summary, Aurora-A kinase is overexpressed in chronic lymphocytic leukemia cells. The expression of acetylated histone H3 suggests that Aurora-A kinase may be active (functional). Thus, Aurora-A kinase overexpression in chronic lymphocytic leukemia may be involved in the genesis of chromosomal abnormalities and is a potential target for therapeutic intervention.
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