白血病起源研究：Lyn酶使B细胞无法凋亡
生物谷报道：B 细胞型慢性淋巴细胞白血病（B－CLL）是成人最常见的白血病类型，其特征是成熟B淋巴细胞在血液中、骨髓和淋巴腺组织中不断积累。人们认为，在发病初期，B-CLL是由于一种尚未清楚的细胞凋亡信号的缺陷导致的。现在，来自意大利帕多瓦大学医学院的Livio Trentin和同事证明B细胞中一种叫做Lyn的酶的表达水平和位置的改变促进了B-CLL的发生。这项研究的相关文章公布在2005年2月1日的Journal of Clinical Investigation上。
研究人员研究了来自40名B-CLL病人的白血病细胞并与正常捐赠者的淋巴细胞进行了比较。他们发现Lyn在CLL细胞中发生了明显的过表达，而且在细胞质中发现了过量的这种酶。另外，这种酶的活性也比正常捐献者细胞的活性水平高。
研究还表明抑制Lyn能够将细胞凋亡过程恢复到正常水平，而且使用能诱导细胞死亡的药物能够同时降低Lyn的表达水平和活性。这意味着高的Lyn活性和B细胞抵制凋亡的能力有直接关系。研究人员认为Lyn与B-CLL的发生有关，并且这种酶也因此成为一种很有潜力的治疗靶标（http://www.bioon.com/）。
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: Journal of Clinical Investigation
- 众说风云 (已有0条评论)
