Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Leuk Lymphoma. 2022 Aug;63(8):1792-1800. doi: 10.1080/10428194.2022.2056175. Epub 2022 Apr 4.
Recent studies in chronic myelomonocytic leukemia (CMML) involving clonal dendritic cell (DC) aggregates and association with systemic immune dysregulation have highlighted novel and potentially targetable pathways of disease progression. CMML DC aggregates are populated by heterogeneous cell types such as CD123 plasmacytoid dendritic cells (pDCs), CD11c + myeloid-derived DCs (mDCs), myeloid-derived suppressor cells (MDSCs), monocytes, and associate with an immune checkpoint called indoleamine 2,3-dioxygenase (IDO). Systemically, these IDO + DC aggregates are associated with immune tolerance marked by regulatory T cell expansion, likely mediated by aberrant DC-T cell interactions occurring within the bone marrow (BM) microenvironment. Somatic mutational events in CMML such as and mutations cooperate to induce T cell exhaustion and contribute toward disease progression to acute myeloid leukemia (AML). In this review, we explore the role of aging-induced alterations in the BM immune microenvironment, aberrant innate immune and proinflammatory signaling, and the adaptive immune system in CMML.
最近的研究表明，慢性髓单核细胞白血病（CMML）中存在克隆树突状细胞（DC）聚集，与全身性免疫失调有关，这突出了疾病进展的新的、潜在的可靶向途径。CMML DC 聚集由异质细胞类型组成，如 CD123 浆细胞样树突状细胞（pDC）、CD11c+髓样来源的 DC（mDC）、髓系来源的抑制细胞（MDSC）、单核细胞，并与一种称为吲哚胺 2,3-双加氧酶（IDO）的免疫检查点相关。在体内，这些 IDO+DC 聚集与免疫耐受有关，其特征是调节性 T 细胞扩增，这可能是由骨髓（BM）微环境中异常的 DC-T 细胞相互作用介导的。CMML 中的体细胞突变事件，如 和 突变，合作诱导 T 细胞衰竭，并导致疾病向急性髓系白血病（AML）进展。在这篇综述中，我们探讨了 BM 免疫微环境中衰老引起的改变、先天免疫和促炎信号的异常以及适应性免疫系统在 CMML 中的作用。
