Ito Masato, Iida Shinsuke, Inagaki Hiroshi, Tsuboi Kazuya, Komatsu Hirokazu, Yamaguchi Motoko, Nakamura Naoya, Suzuki Ritsuro, Seto Masao, Nakamura Shigeo, Morishima Yasuo, Ueda Ryuzo
Second Department of Internal Medicine, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601.
Jpn J Cancer Res. 2002 Jun;93(6):685-94. doi: 10.1111/j.1349-7006.2002.tb01307.x.
B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.
B细胞慢性淋巴细胞白血病(B-CLL)/小淋巴细胞淋巴瘤(SLL)由多种异质性疾病组成,这些疾病通过形态学、免疫表型和分子特征来区分。MUM1(多发性骨髓瘤致癌基因1)是一种原癌基因,在多发性骨髓瘤中由于(6;14)(p25;q32)染色体易位而失调,并且在多种恶性淋巴瘤实体中也有表达。我们检测了MUM1在B-CLL / SLL中的表达,通过免疫组织化学分析发现,4个源自B-CLL的细胞系中有2个以及29例患者标本中有14例表达MUM1。MUM1表达与CD38表达、免疫球蛋白重链基因可变区(IgV(H))的体细胞超突变或患者的任何其他临床特征均无关联。有趣的是,MUM1阳性的患者总生存时间比MUM1阴性的患者短(50%生存率:22个月对82个月)(P = 0.0008,对数秩检验)。Cox比例风险回归模型的多变量分析显示,MUM1表达和未突变的IgV(H)状态是B-CLL / SLL患者独立的不良预后因素。这些发现表明,MUM1表达是B-CLL / SLL中一个有用的预后因素。为了开发针对预后不良亚型患者的治疗方法,需要阐明MUM1在B-CLL / SLL中的生物学作用和作用机制。