Unraveling unique features of plasma cell clones in POEMS syndrome with single-cell analysis.
Unraveling unique features of plasma cell clones in POEMS syndrome with single-cell analysis.
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DOI：
10.1172/jci.insight.151482
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发表时间：
2022-10-24
期刊：
影响因子：
8
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
--
作者：
Isshiki, Yusuke;Oshima, Motohiko;Mimura, Naoya;Kayamori, Kensuke;Miyamoto-Nagai, Yurie;Seki, Masahide;Nakajima-Takagi, Yaeko;Kanamori, Takashi;Iwamoto, Eisuke;Muto, Tomoya;Tsukamoto, Shokichi;Takeda, Yusuke;Ohwada, Chikako;Misawa, Sonoko;Ikeda, Jun-Ichiro;Sanada, Masashi;Kuwabara, Satoshi;Suzuki, Yutaka;Sakaida, Emiko;Nakaseko, Chiaki;Iwama, Atsushi
POEMS综合征是一种罕见的单克隆浆细胞疾病，具有不同于其他浆细胞肿瘤的独特症状，包括高血清VEGF水平。由于POEMS克隆的预期分离尚未成功，它们的真实的性质仍然不清楚。在此，我们对POEMS综合征患者的BM浆细胞进行了单细胞RNA-Seq，并鉴定了具有IG λ轻链（IGL）序列（IGLV 1 -36、-40、-44和-47）的POEMS克隆，这些序列具有POEMS综合征特异性氨基酸变化。浆细胞中POEMS克隆的比例明显小于多发性骨髓瘤（MM）和意义不明的单克隆丙种球蛋白病（MGUS）患者。单细胞转录组显示POEMS克隆是CD 19+、CD 138+和MHC IIlo类，这允许它们的前瞻性分离。POEMS克隆表达的c-MYC和CCND 1水平显著低于MM克隆，这是其体积小的原因。VEGF mRNA在POEMS克隆中未上调，直接表明VEGF不由POEMS克隆产生。这些结果揭示了POEMS克隆的独特特征，并增强了我们对POEMS综合征发病机制的理解。
POEMS syndrome is a rare monoclonal plasma cell disorder, with unique symptoms distinct from those of other plasma cell neoplasms, including high serum VEGF levels. Because the prospective isolation of POEMS clones has not yet been successful, their real nature remains unclear. Herein, we performed single-cell RNA-Seq of BM plasma cells from patients with POEMS syndrome and identified POEMS clones that had Ig λ light chain (IGL) sequences (IGLV1-36, -40, -44, and -47) with amino acid changes specific to POEMS syndrome. The proportions of POEMS clones in plasma cells were markedly smaller than in patients with multiple myeloma (MM) and patients with monoclonal gammopathy of undetermined significance (MGUS). Single-cell transcriptomes revealed that POEMS clones were CD19+, CD138+, and MHC class IIlo, which allowed for their prospective isolation. POEMS clones expressed significantly lower levels of c-MYC and CCND1 than MM clones, accounting for their small size. VEGF mRNA was not upregulated in POEMS clones, directly indicating that VEGF is not produced by POEMS clones. These results reveal unique features of POEMS clones and enhance our understanding of the pathogenesis of POEMS syndrome.
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