Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
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DOI：
10.1038/s41408-019-0262-0
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发表时间：
2019-12-06
影响因子：
12.8
通讯作者：
Pemmaraju, Naveen
中科院分区：
文献类型：
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作者：
Beird, Hannah C.;Khan, Maliha;Pemmaraju, Naveen
母浆细胞样树突状细胞肿瘤（BPDCN）是一种罕见的、以男性为主的血液系统恶性肿瘤，预后较差，最近只有一种获批的药物（tagraxofusp）。它的特点是前体浆细胞样树突状细胞（pDCs）的异常增殖，在骨髓和外周血中的表现与急性髓性白血病（AML）和骨髓增生异常综合征(MDS)/慢性髓单核细胞白血病（CMML）的形态和分子相似。为了确定BPDCN的疾病特异性分子特征，我们使用内部血液恶性肿瘤面板（“T300”面板）、转录组微阵列和血清多重免疫分析分析了原发性患者样本的骨髓、外周血和血清样本。TET2突变（5/ 8,63 %）在我们的队列中最为普遍。利用转录组芯片，我们发现，与AML样本相比，BPDCN中pDCs特异性基因（lamp、CCDC50）的表达水平更高。最后，血清细胞因子谱分析显示，与AML相比，BPDCN中嗜酸性趋化剂eotaxin和RANTES水平显著升高。随着高水平的PTPRS和肿瘤细胞的树突状性质，这些发现表明这种疾病可能存在炎症前背景，其中BPDCN具有非活化的pDCs。
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant hematologic malignancy with poor outcomes and with just one recently approved agent (tagraxofusp). It is characterized by the abnormal proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled the bone marrow, peripheral blood, and serum samples from primary patient samples using an in-house hematologic malignancy panel ("T300" panel), transcriptome microarray, and serum multiplex immunoassays. TET2 mutations (5/8, 63%) were the most prevalent in our cohort. Using the transcriptome microarray, genes specific to pDCs (LAMPS, CCDC50) were more highly expressed in BPDCN than in AML specimens. Finally, the serum cytokine profile analysis showed significantly elevated levels of eosinophil chemoattractants eotaxin and RANTES in BPDCN as compared with AML. Along with the high levels of PTPRS and dendritic nature of the tumor cells, these findings suggest a possible pre-inflammatory context of this disease, in which BPDCN features nonactivated pDCs.