生物谷報(bào)道：B 細(xì)胞型慢性淋巴細(xì)胞白血病（B－CLL）是成人最常見(jiàn)的白血病類(lèi)型,，其特征是成熟B淋巴細(xì)胞在血液中,、骨髓和淋巴腺組織中不斷積累,。人們認(rèn)為，在發(fā)病初期,，B-CLL是由于一種尚未清楚的細(xì)胞凋亡信號(hào)的缺陷導(dǎo)致的?，F(xiàn)在，來(lái)自意大利帕多瓦大學(xué)醫(yī)學(xué)院的Livio Trentin和同事證明B細(xì)胞中一種叫做Lyn的酶的表達(dá)水平和位置的改變促進(jìn)了B-CLL的發(fā)生,。這項(xiàng)研究的相關(guān)文章公布在2005年2月1日的Journal of Clinical Investigation上,。
研究人員研究了來(lái)自40名B-CLL病人的白血病細(xì)胞并與正常捐贈(zèng)者的淋巴細(xì)胞進(jìn)行了比較。他們發(fā)現(xiàn)Lyn在CLL細(xì)胞中發(fā)生了明顯的過(guò)表達(dá),，而且在細(xì)胞質(zhì)中發(fā)現(xiàn)了過(guò)量的這種酶,。另外，這種酶的活性也比正常捐獻(xiàn)者細(xì)胞的活性水平高,。
研究還表明抑制Lyn能夠?qū)⒓?xì)胞凋亡過(guò)程恢復(fù)到正常水平,，而且使用能誘導(dǎo)細(xì)胞死亡的藥物能夠同時(shí)降低Lyn的表達(dá)水平和活性。這意味著高的Lyn活性和B細(xì)胞抵制凋亡的能力有直接關(guān)系,。研究人員認(rèn)為L(zhǎng)yn與B-CLL的發(fā)生有關(guān),，并且這種酶也因此成為一種很有潛力的治療靶標(biāo)（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
