白血病由造血干细胞/祖细胞 (HSPC) 的反复克隆突变引起，这些突变会导致骨髓微环境 (BMM) 发生深刻变化，有利于白血病干细胞 (LSC) 的生长，而不是正常 HSPC。了解白血病前期突变 HSPC 和 BMM 之间的相互作用对于开发预防白血病发生的新治疗策略至关重要。我们假设白血病前期 LSC (pLSC) 会诱导对白血病发生至关重要的 BMM 变化。使用我们的 AML 小鼠模型，我们对白血病前期 BMM (pBMM) 细胞进行了单细胞 RNA 测序。我们发现正常 HSC (nHSC) 调节的 LepR 间充质干细胞和内皮细胞减少，同时 CD55 成纤维细胞和周细胞增加。白血病前 CD55 成纤维细胞具有较高的增殖率和减少的胶原蛋白表达，表明白血病发生过程中细胞外基质的重塑。重要的是，共培养检测发现白血病前期 CD55 成纤维细胞的 pLSC 扩增显着超过 nHSC。总之，我们确定了一种独特的 pBMM 和一种新的 CD55 成纤维细胞群体，该群体在 pBMM 中扩展，可促进 pLSC 相对于 nHSC 的适应性。© 2024。作者。

Leukemias arise from recurrent clonal mutations in hematopoietic stem/progenitor cells (HSPCs) that cause profound changes in the bone marrow microenvironment (BMM) favoring leukemic stem cell (LSC) growth over normal HSPCs. Understanding the cross talk between preleukemic mutated HSPCs and the BMM is critical to develop novel therapeutic strategies to prevent leukemogenesis. We hypothesize that preleukemic-LSCs (pLSCs) induce BMM changes critical for leukemogenesis. Using our AML-murine model, we performed single-cell RNA-sequencing of preleukemic BMM (pBMM) cells. We found normal HSC (nHSC)-regulating LepR+ mesenchymal stem cells, and endothelial cells were decreased, along with increases in CD55+ fibroblasts and pericytes. Preleukemic CD55+ fibroblasts had higher proliferation rates and decreased collagen expression, suggesting extracellular matrix remodeling during leukemogenesis. Importantly, co-culture assays found preleukemic CD55+ fibroblasts expanded pLSCs significantly over nHSCs. In conclusion, we have identified a distinct pBMM and a novel CD55+ fibroblast population that is expanded in pBMM that promote fitness of pLSCs over nHSCs.© 2024. The Author(s).