克隆性造血在克隆上与多发性骨髓瘤无关,与特定的微环境变化有关。

IF 21 1区 医学 Q1 HEMATOLOGY
Blood Pub Date : 2025-03-20 DOI:10.1182/blood.2024026236
Marta Lionetti, Margherita Scopetti, Antonio Matera, Akihiro Maeda, Alessio Marella, Francesca Lazzaroni, Giancarlo Castellano, Sonia Fabris, Stefania Pioggia, Silvia Lonati, Alfredo Marchetti, Alessandra Cattaneo, Marta Tornese, Antonino Neri, Claudia Leoni, Loredana Pettine, Valentina Traini, Ilaria Silvestris, Marzia Barbieri, Giuseppina Fabbiano, Domenica Ronchetti, Elisa Taiana, Claudio De Magistris, Matteo Claudio Da Via', Francesco Passamonti, Niccolò Bolli
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引用次数: 0

摘要

多发性骨髓瘤(MM)的发病是由基因组事件决定的。然而,多发性骨髓瘤从无症状阶段发展到最终对治疗无效的侵袭性疾病,还取决于肿瘤微环境(TME)的变化。具有不确定潜能的克隆性造血(CHIP)是造血干细胞的一种普遍克隆情况,它的存在与更加炎症的微环境有因果关系。在这里,我们在106名MM患者中发现,CHIP在诊断时经常与MM并存,与更晚期的R-ISS分期、更高的年龄相关,并显示出中位血红蛋白降低的非显著趋势。在我们的队列中,这两种疾病没有共同的克隆起源。16 名 MM 患者的单细胞 RNA 序列分析显示,当出现 CHIP 时,TME 会发生显著变化:幼稚 T 细胞减少,TME 促炎,树突状细胞的抗原递呈功能降低,CD8 细胞表达衰竭标记。推断 CHIP 阳性 TME 中细胞类型之间的相互作用表明,尤其是单核细胞、T 细胞和克隆浆细胞可能在介导炎症、免疫逃避和有利于 MM 细胞的促生存信号方面起着重要作用。总之,我们的数据表明,在存在 CHIP 的情况下,MM 诊断时的 TME 受到了严重破坏,这与通常在晚期疾病中看到的情况一致,具有潜在的转化意义。我们的数据强调了这种关联的相关性,并促使我们进一步研究 CHIP 在 MM TME 中的调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal hematopoiesis is clonally unrelated to multiple myeloma and is associated with specific microenvironmental changes.

Multiple myeloma (MM) initiation is dictated by genomic events. However, its progression from asymptomatic stages to an aggressive disease that ultimately fails to respond to treatments is also dependent on changes of the tumor microenvironment (TME). Clonal hematopoiesis of indeterminate potential (CHIP) is a prevalent clonal condition of the hematopoietic stem cell whose presence is causally linked to a more inflamed microenvironment. Here, we show in 106 patients with MM that CHIP is frequently co-existing with MM at diagnosis, associates with a more advanced R-ISS stage, higher age and shows a non-significant trend towards lower median hemoglobin. In our cohort the two conditions do not share a clonal origin. Single cell RNA-sequencing in 16 MM patients highlights significant TME changes when CHIP is present: decreased naïve T cells, a pro-inflammatory TME, decreased antigen-presenting function by dendritic cells and expression of exhaustion markers in CD8 cells. Inferred interactions between cell types in CHIP-positive TME suggested that especially monocytes, T cells and clonal plasma cells may have a prominent role in mediating inflammation, immune evasion and pro-survival signals in favor of MM cells. Altogether, our data show that, in the presence of CHIP, the TME of MM at diagnosis is significantly disrupted in line with what usually seen in more advanced disease, with potential translational implications. Our data highlight the relevance of this association and prompt for further studies on the modifier role of CHIP in the MM TME.

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来源期刊
Blood
Blood 医学-血液学
CiteScore
23.60
自引率
3.90%
发文量
955
审稿时长
1 months
期刊介绍: Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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