CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis
CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis
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DOI：
10.1038/sj.leu.2403671
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发表时间：
2005-04-01
期刊：
影响因子：
11.4
通讯作者：
Grossi, CE
中科院分区：
文献类型：
--
作者：
Fais, F;Tenca, C;Grossi, CE
急性淋巴细胞性白血病(ALL)是儿童最常见的恶性肿瘤。尽管在治疗方面取得了进展，但一些所有亚群的患者仍然表现不佳。CD1d是一种单态分子，由于糖脂-α-半乳糖神经酰胺(α-GalCer)的特性，CD1d是一个合适的免疫治疗靶点，它能够被呈递给CD1d限制性T细胞，具有细胞毒活性。我们研究了80例根据免疫表型、细胞遗传学特征和发病年龄定义的儿童B细胞前体(BCP)ALL病例中CD1d的表达。CD1d在15%的患者所有细胞上均有表达。CD1d(+)ALL与婴幼儿白血病、前B表型、混合细胞性白血病(MLL)/AF4基因重排显著相关。因此，CD1d(+)ALL患者的总体生存时间显著缩短。CD1d(+)白血病细胞能通过CD1d向细胞毒性CD1d限制性T细胞递送α-GalCer，诱导ALL细胞凋亡，而CD1d单抗可抑制CD1d诱导的ALL细胞凋亡。负载α-GalCer的CD1d(+)细胞可诱导CD1d限制性T细胞分泌细胞因子。对正常供者骨髓(BM)细胞的分析表明，CD19(+)/CD1d(+)细胞多为成熟B淋巴细胞。少数BCP表达CD1d。因此，CD1d在所有病例中的表达预示着不良预后，但可能提供一种治疗工具。
Acute lymphoblastic leukemia ( ALL) is the most frequent malignancy of childhood. Although therapeutical advances have been achieved, some ALL subgroups still fare poorly. CD1d is a monomorphic molecule that provides a suitable target for immunotherapy in view of the characterization of a glycolipid, alpha-galactosylceramide (alpha-GalCer), capable of being presented to CD1d-restricted T cells with cytotoxic potential. We investigated CD1d expression in 80 pediatric B-cell precursor (BCP) ALL cases defined according to immunophenotype, cytogenetic features and age at onset. CD1d was detected on ALL cells in 15% of the patients. CD1d(+) ALLs were significantly associated with infant leukemia, pro-B phenotype and mixed-lineage leukemia (MLL)/AF4 gene rearrangement. Accordingly, overall survival of patients with CD1d(+) ALL was significantly shorter. CD1d(+) leukemic blasts were able to present alpha-GalCer via CD1d to cytotoxic CD1d-restricted T cells, which induced apoptosis of ALL cells that was inhibited by mAb to CD1d. CD1d(+) blasts loaded with alpha-GalCer elicited cytokine secretion by CD1d-restricted T cells. Analysis of bone marrow ( BM) cells derived from normal donors revealed that CD19(+)/CD1d(+) cells were mostly mature B lymphocytes. However, a minority of BCPs expressed CD1d. Thus, expression of CD1d in ALL cases heralds an adverse prognosis but may provide a therapeutic tool.