Sanz Laura, Garcia-Marco José A, Casanova Benito, de La Fuente María Teresa, García-Gila Mercedes, Garcia-Pardo Angeles, Silva Augusto
Departamento de Inmunología, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):562-7. doi: 10.1016/j.bbrc.2004.01.095.
Malignant cell accumulation in B-cell chronic lymphocytic leukemia (B-CLL) is primarily caused by defective apoptosis rather than increased proliferation. To further understand the role of Bcl-2 family members, known regulators of apoptosis, in the abnormal B-CLL survival, we have measured their mRNA levels in fresh B-CLL cells and in cultures undergoing spontaneous apoptosis. Using RNA protection assays we found constitutive expression of most bcl-2 members with high levels of bcl2, bcl-w, bad, bak, bax, and the bcl-2/bax ratio, compared to normal PBL. Spontaneous apoptosis of B-CLL cells by in vitro culture resulted in decreased bcl-2, bcl-w, bfl-1, mcl-1, bak, bax, and bcl-2/bax expression. The pro-apoptotic member bik was only expressed in 5/19 cases and was not modulated during apoptosis, suggesting that bik is not involved in this process. Thus, several Bcl-2 family genes are regulated during B-CLL spontaneous apoptosis and their relative levels may contribute to in vivo progression of the disease.
B细胞慢性淋巴细胞白血病（B-CLL）中恶性细胞的积累主要是由凋亡缺陷而非增殖增加引起的。为了进一步了解凋亡的已知调节因子Bcl-2家族成员在B-CLL异常存活中的作用，我们检测了它们在新鲜B-CLL细胞和自发凋亡培养物中的mRNA水平。使用RNA保护分析，我们发现与正常外周血淋巴细胞（PBL）相比，大多数bcl-2家族成员组成性表达，其中bcl2、bcl-w、bad、bak、bax以及bcl-2/bax比值水平较高。体外培养导致B-CLL细胞自发凋亡，从而使bcl-2、bcl-w、bfl-1、mcl-1、bak、bax以及bcl-2/bax的表达降低。促凋亡成员bik仅在19例中的5例中表达，且在凋亡过程中未被调节，这表明bik不参与此过程。因此，在B-CLL自发凋亡过程中，几个Bcl-2家族基因受到调节，它们的相对水平可能有助于该疾病的体内进展。
