Department of Pediatrics, Comprehensive Bone Marrow Failure Center, Division of Hematology, Children's Hospital of Philadelphia, PA 19104, USA.
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, PA 19104, USA.
Oncotarget. 2024 Sep 4;15:609-613. doi: 10.18632/oncotarget.28642.
Lifelong hematopoiesis is sustained by crosstalk between hematopoietic stem and progenitor cells (HSPCs) and specialized bone marrow niches. Acute myeloid leukemia (AML) upends that balance, as leukemic blasts secrete factors that remodel the bone marrow into a self-reinforcing leukemic niche. The inflammatory secretome behind this compartmental adaptation accounts for a progressive decline in hematopoietic function that leads to diagnosis and persists through early treatment. Not surprisingly, the mediators of an acute inflammatory injury and HSPC suppression have attracted much attention in an effort to alleviate morbidity and improve outcomes. HSPCs typically recover during disease remission and re-expand in the bone marrow (BM), but little is known about potentially lasting consequences for stem cells and progenitors. We recently showed that AML-experienced HSPCs actively participate in the inflammatory process during leukemic progression. HSPCs are constituent components of the innate immune system, and elegant studies of infection and experimental inflammation over the past decade have described the generation of an adoptively transferable, innate immune memory. Building on this paradigm, we discuss the potential translational relevance of a durable legacy in AML-experienced HSPC.
长期的造血作用是由造血干细胞和祖细胞（HSPCs）与专门的骨髓龛之间的相互作用维持的。急性髓系白血病（AML）打破了这种平衡，因为白血病细胞会分泌因子，将骨髓重塑为自我强化的白血病龛。这种隔室适应背后的炎症分泌组解释了造血功能的逐渐下降，导致诊断，并在早期治疗中持续存在。毫不奇怪，急性炎症损伤和 HSPC 抑制的介质引起了人们的广泛关注，以期减轻发病率并改善预后。HSPCs 在疾病缓解期间通常会恢复，并且在骨髓（BM）中重新扩增，但对于干细胞和祖细胞可能存在持久的后果知之甚少。我们最近表明，AML 经历的 HSPCs 在白血病进展过程中积极参与炎症过程。HSPCs 是固有免疫系统的组成部分，过去十年中对感染和实验性炎症的精心研究描述了可采用的先天免疫记忆的产生。在此基础上，我们讨论了 AML 经历的 HSPC 中持久遗产的潜在转化相关性。
