CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin
CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin
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DOI：
10.1182/blood.v89.6.2048
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发表时间：
1997-03-15
期刊：
影响因子：
20.3
通讯作者：
Pinto, A
中科院分区：
文献类型：
--
作者：
Gattei, V;Degan, M;Pinto, A
CD 30配体（CD 30 L）是一种II型膜糖蛋白，能够通过其特异性的反向结构CD 30转导导致细胞死亡或增殖的信号。尽管一些证据表明CD 30 L作为旁分泌或自分泌作用的表面分子在霍奇金病的失调的细胞因子级联中起关键作用，关于其在其他人类造血系统恶性肿瘤中的分布和生物学意义知之甚少。通过对181例患者的肿瘤细胞进行RNA研究和抗CD 30 L单克隆抗体M80的免疫染色分析，我们能够显示不同谱系和成熟阶段的人类造血系统恶性肿瘤显示配体的频繁和广泛表达。在60%的急性髓性白血病（AML）、54%的B系急性淋巴细胞白血病（ALL）和68%的B细胞淋巴增生性疾病中检测到CD 30 L mRNA和表面蛋白。在后一组中，毛细胞白血病和高级别B细胞非霍奇金淋巴瘤（B-NHL）与B细胞慢性淋巴细胞白血病和低级别B-NHL相比表达更高的表面密度的CD 30 L。从一部分多发性骨髓瘤患者中纯化的浆细胞也显示出CD 30 L mRNA和蛋白。在T细胞肿瘤中发现CD 30 L的表达更受限制，其主要限于具有活化的外周T细胞表型的肿瘤，例如T细胞幼淋巴细胞白血病、外周T-NHL和成人T细胞白血病/淋巴瘤。相比之下，所分析的T谱系ALL均不表达配体。在AML中，在法国-美国-英国M3、M4和M5表型中检测到高细胞密度的CD 30 L，其与肿瘤细胞上某些表面结构的存在直接相关，包括p55白细胞介素-2受体α链、β 2整联蛋白的α（M）（CD 11b）链和细胞间粘附分子-1（CD 54），对正常造血细胞的分析证明，除了循环和扁桃体B细胞外，一部分骨髓前体细胞、成红细胞和巨核细胞亚群也表达CD 30 L。最后，我们已经表明，在原代白血病细胞上表达的天然CD 30 L通过触发CD 30（+）靶细胞上的促有丝分裂和抗增殖信号而具有功能活性。与CD 30 L相反，181例原发性肿瘤中仅10例表达CD 30 mRNA或蛋白，因此在人类造血肿瘤中不太可能存在CD 30-CD 30 L自分泌环。总之，我们的数据表明，CD 30 L广泛表达，从早期到晚期的人类造血，并建议该分子的调节作用，在正常和恶性造血细胞与CD 30（+）免疫效应和/或微环境辅助细胞的相互作用。(C)1997年，美国血液学会。
CD30 ligand (CD30L) is a type-ii membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30, Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta 2 integrins, and the intercellular adhesion molecule-1 (CD54), Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30(+) target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30(+) immune effecters and/or microenvironmental accessory cells. (C) 1997 by The American Society of Hematology.