Enzyme allows B cells to resist death, leading to leukemia
B cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in adults and is characterized by the progressive accumulation of mature B lymphocytes in the blood, bone marrow, and lymphatic tissues. It is believed that in the early stages of disease, B-CLL is the result of an undefined defect in the programmed signals that trigger normal B cell death (apoptosis). Livio Trentin and colleagues from Padua University School of Medicine now demonstrate that high levels of expression and altered cellular location of an enzyme in B cells known as Lyn, contributes to the development of B-CLL.
The authors examined leukemia cells from 40 patients with B-CLL and compared them with lymphocytes from normal donors. They found that Lyn was markedly overexpressed in CLL cells and an unusual amount of the enzyme was found in the cell cytosol. In addition, the enzyme was constantly active compared with levels of activity in normal donor cells.
The authors went on to show that inhibition of Lyn was able to restore the process of cell apoptosis to normal and treatment of malignant cells with drugs that induce cell death decreased both Lyn expression levels and activity – suggesting a direct correlation between high Lyn activity and the ability of these B cells to resist apoptosis. The authors suggest that Lyn is involved in the development of B-CLL and that this enzyme therefore represents an attractive target for therapy.
The study will appear online on January 13 in advance of publication in the February 1 print edition of the Journal of Clinical Investigation.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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