Harada N, Hata H, Yoshida M, Soniki T, Nagasaki A, Kuribayashi N, Kimura T, Matsuzaki H, Mitsuya H
Second Department of Internal Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Leukemia. 1998 Nov;12(11):1817-20. doi: 10.1038/sj.leu.2401168.
Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X(L), Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X(L) were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X(L). Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X(L) tended to be expressed in samples from cases at advanced clinical stage. Bcl-X(L) was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X(L) and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X(L) although Bcl-X(L) tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X(L) and Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.
Bcl-2蛋白家族成员，包括Bcl-2、Bcl-X(L)、Bcl-Xs和Bax，被认为在细胞凋亡调节和耐药性方面发挥重要作用。为了解这些蛋白在新鲜人骨髓瘤细胞中的意义，采用蛋白质印迹法分析了17例多发性骨髓瘤（MM）患者和3例浆细胞白血病（PCL）患者中Bcl-2蛋白家族的表达情况。分别在12个和9个样本中检测到Bcl-2和Bcl-X(L)。所有PCL病例均显示Bcl-2和Bcl-X(L)共表达。MM病例分析显示，Bcl-2优先在临床早期病例的样本中表达，而Bcl-X(L)倾向于在临床晚期病例的样本中表达。Bcl-X(L)在有髓外病变病例的肿瘤细胞中显著表达。Bcl-2或Bcl-X(L)的表达水平与先前的化疗之间无相关性。仅在1例因骨髓瘤细胞浸润导致胸腔积液且血清乳酸脱氢酶水平高的患者中发现Bax表达。生存分析显示，尽管Bcl-X(L)倾向于在预后较差的病例中表达，但Bcl-2或Bcl-X(L)的表达无统计学意义。这些发现表明，Bcl-2蛋白家族在新鲜骨髓瘤细胞中的表达受到异质性调节。Bcl-X(L)和Bcl-2的表达可能分别与髓外浸润和疾病早期相关。骨髓瘤细胞中缺乏Bax可能导致骨髓瘤细胞对抗癌药物的低敏感性，因为据报道Bax介导某些抗癌药物的细胞毒性。
