DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis
DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis
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DOI：
10.1172/jci118486
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发表时间：
1996-02-01
影响因子：
15.9
通讯作者：
Nomura, T
中科院分区：
文献类型：
--
作者：
Inokuchi, K;Miyake, K;Nomura, T
应用流式细胞术和免疫沉淀法（IF）检测了16例正常人、17例骨髓增生异常综合征（MDS）患者和10例急性髓性白血病（AML）患者骨髓（BM）和外周血（PB）细胞中结肠癌缺失（DCC）蛋白的表达。DCC蛋白表达率为6.6 ~ 57.0%。双色流式细胞术显示，在BM-MNCs中，DCC蛋白在CD 14+、CD 13+和因子8+细胞上清楚地表达，而在CD 19+和CD 7+细胞上表达较低，并且在CD 34+、CD 8+和血型糖蛋白A+细胞上不表达。此外，在PB CD 11b+和CD 13+细胞上未观察到DCC蛋白表达。免疫组化结果显示，DCC胞外区特异性抗体AF 5和胞浆区特异性抗体G97-449在骨髓和外周血单个核细胞上均检测到180 kD DCC蛋白，而流式细胞术在任何BM-MNC MDS谱系（0.1-1.5%）或AML白血病细胞（0.1-0.9%）上均未检测到DCC蛋白。免疫组化结果显示，AF 5抗体在5例MDS患者中的3例和5例AML患者中的4例的BM-MNC上均未检测到DCC蛋白;然而，G97-449抗体在两个MDS患者中检测到180-kDDCC蛋白，其中AF 5检测到DCC条带大大减少。这些发现表明DCC蛋白的存在似乎与正常的造血有关，BM-MNCs和AML细胞表面的缺失可能与MDS和AML的发病机制有关。
Using flow cytometry and immunoprecipitation (IF), we have investigated the deleted in colon cancer (DCC) protein expression on the bone marrow (BM) and peripheral blood (PB) cells of 16 normal subjects, 17 myelodysplastic syndrome (MDS) patients, and 10 acute myelogenous leukemia (AML) patients.With regard to the BM mononuclear cells (BM-MNCs) of normal subjects, the DCC protein expression ranged from 6.6 to 57.0%. Two-color flow cytometry revealed that among the BM-MNCs the DCC protein was clearly expressed on the CD14+, CD13+, and factor 8+ cells, whereas it was low on the CD19+ and CD7+ cells and did nor express on the CD34+, CD8+, and the glycophorin A+ cells. Further, the DCC protein expression was not seen on the PB CD11b+ and CD13+ cells. The IP results revealed that the 180-kD DCC protein was detected on the MNCs of both the BM and PB cells by the antibodies AF5, specific for the DCC extracellular domain, and G97-449, specific for the cytoplasmic domain.In contrast, flow cytometry did not detect the DCC protein on any BM-MNC MDS lineages (0.1-1.5%) or on AML leukemic cells (0.1-0.9%). The IP results indicated that the AF5 antibody did not detect the DCC protein on BM-MNCs of three of five MDS patients and four of five AML patients; however, the G97-449 antibody detected the 180-kD DCC protein in two MDS patients in whom AF5 had detected greatly reduced DCC band.These findings suggest that the DCC protein presence appears to be associated with normal hematopoiesis, and that its absence on the surfaces of the BM-MNCs and AML cells may contribute to the MDS and AML pathogenesis.