Frequent expression of the variant CD30 in human malignant myeloid and lymphoid neoplasms
Frequent expression of the variant CD30 in human malignant myeloid and lymphoid neoplasms
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DOI：
10.1016/s0002-9440(10)65522-8
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发表时间：
1999-12-01
影响因子：
6
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Horie, R;Gattei, V;Watanabe, T
我们之前发现了 CD30 (CD30v) 的一个变体，它只保留了真正 CD30 的细胞质区域。该变体在肺泡巨噬细胞中表达。 CD30v可以像CD30一样激活核因子-κB（NF-κB），并且其在HL-60中的过度表达诱导分化表型。为了更好地了解 CD30v 的生理和病理功能，我们使用多种方法检查了 238 个人类恶性骨髓和淋巴肿瘤样本，检查了该变体的表达。通过逆转录聚合酶链式反应 (RT-PCR) 进行的筛选显示，在急性髓性白血病 (AML)、骨髓增殖性疾病 (MBC) 的髓样母细胞危象以及 B 和 T 细胞起源的淋巴增殖性疾病 (LPD) 的 72 个样本中，分别有 52 个、11 个中的 7 个、90 个样本中的 63 个和 30 个样本中存在 CD30v 转录物的表达。 CD30v在单核细胞导向的AML（FAB M4和M5）、B-tell慢性淋巴细胞白血病（B-CLL）和多发性骨髓瘤（MM）中高表达，使用用对应于氨基末端CD30v的9个氨基酸的肽制备的特异性抗体HCD30C2，在25个AML和ALL样本中的10个和10个AML和ALL样本中检测到CD30v蛋白的表达，分别。在 AML 中，CD30v 的免疫细胞化学检测揭示了松散的 CD30v 表达细胞簇的存在，分散在 CD30v 阴性母细胞群中。最后，在选定的 AML 和 LPD 病例中，通过 Northern 和 Western blotting 证实了 CD30v mRNA 和蛋白的平行表达。 AML 和 LPD 中 CD30v 和 CD30 配体转录物的表达之间发现显着相关性（P = 0.02，比值比 = 3.2）。 CD30v 与信号转导蛋白、肿瘤坏死因子受体相关因子 (TRAF) 2 和 TRAF5 的关联通过免疫共沉淀分析得到证实，正如真实的 CD30 蛋白所证实的那样。 RT-PCR 证实，在表达 CD30v 的白血病母细胞中注意到 TRAF1、TRAF2、TRAF3 和 TRAF5 转录本的表达。总的来说，CD30V 与 TRAF 蛋白在骨髓和淋巴来源的人类肿瘤细胞中的频繁表达为该蛋白在多种骨髓和淋巴细胞的生长和分化中的生物学和可能的病理功能提供了支持性证据。
We earlier identified a variant of CD30 (CD30v) that retains only the cytoplasmic region of the authentic CD30. This variant is expressed in alveolar macrophages. CD30v can activate the nuclear factor-kappa B (NF-kappa B) as CD30, and its overexpression in HL-60 induced a differentiated phenotype. To better understand the physiological and pathological functions of CD30v, expression of this variant was examined using a multiple approach to examine 238 samples of human malignant myeloid and lymphoid neoplasms. Screening by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of CD30v transcripts in 52 of 72, 7 of 11, 63 of 90, and 7 of 30 samples of acute myeloid leukemia (AML), myeloid blast crisis of myeloproliferative disorders (MBC), and lymphoproliferative disorders (LPDs) of B- and T-cell origin, respectively. CD30v expression was high in monocyte-oriented AMLs (FAB M4 and M5), B-tell chronic lymphocytic leukemia (B-CLL), and multiple myeloma (MM), Using the specific antibody HCD30C2, prepared using a peptide corresponding to the nine amino acids of the amino-terminal CD30v, expression of CD30v protein was detected in 10 of 25 and 2 of 10 AML and ALL samples, respectively. In AMLs, immunocytochemical detection of CD30v revealed the presence of loose clusters of CD30v-expressing cells dispersed amid a population of CD30v-negative blasts. Finally, the parallel expression of CD30v mRNA and protein, as evidenced by Northern and Western blotting,was confirmed in selected cases of AMLs and LPDs. A significant correlation was found between expressions of CD30v and CD30 ligand transcripts in AML and LPD (P = 0.02, odds ratio = 3.2). The association of CD30v with signal-transducing proteins, tumor necrosis factor receptor-associated factor (TRAF) 2, and TRAF5 was demonstrated by coimmunoprecipitation analysis, as was demonstrated for authentic CD30 protein. Expression of transcripts for TRAF1, TRAF2, TRAF3, and TRAF5, as demonstrated by RT-PCR, was noted in leukemic blasts that express CD30v, Collectively, frequent expression of CD30V along with TRAF proteins in human neoplastic cells of myeloid and lymphoid origin provide supportive evidence for biological and possible pathological functions of this protein in the growth and differentiation of a variety of myeloid and lymphoid cells.