骨髓纤维化（MF）是一种复杂的骨髓增殖性肿瘤，其特征是异常的造血干细胞增殖和随后的骨髓（BM）纤维化。 MF 首次被记录于 19 世纪末，此后人们对其进行了广泛的研究，以阐明其病理生理学、临床表型和治疗干预措施。 MF 可分为原发性和继发性两种形式，两者均由 JAK2、CALR 和 MPL 等基因突变驱动，这些基因激活 JAK-STAT 信号通路。这些驱动突变经常伴随着 TET2、SRSF2 和 TP53 等基因中的其他非驱动突变，从而导致疾病的复杂性。骨髓微环境由基质细胞、细胞外基质和细胞因子（如 TGF-β 和 TNF-α）组成，在纤维化和异常造血中发挥着关键作用。临床上，MF 的症状包括贫血、脾肿大、疲劳以及白血病转化等严重并发症。由髓外造血引起的脾肿大会导致腹部不适和早饱感。目前的治疗策略包括 JAK 抑制剂（如 Ruxolitinib），其靶向 JAK-STAT 通路，以及支持治疗，如输血、红细胞生成刺激剂和开发组合方法。异基因造血干细胞移植仍然是唯一的治疗选择，尽管它仅限于年轻、高危患者。最近批准的 JAK 抑制剂，包括 Fedratinib、Pacritinib 和 Momelotinib，扩大了治疗领域。空间解析转录组学 (SRT) 彻底改变了组织空间背景下基因表达的研究，为细胞异质性、空间基因调控和微环境相互作用（包括基质造血动力学）提供了前所未有的见解。 SRT 能够对 BM 和脾脏中的基因表达进行高分辨率绘图，揭示分子特征、空间异质性和驱动疾病进展的病理生态位。这些技术阐明了脾脏在 MF 中的作用，强调其转变为异常造血活动、纤维化变化和免疫细胞浸润的部位，充当“肿瘤替代品”。通过分析 BM 和脾脏内的不同细胞群和分子变化，SRT 有助于更深入地了解 MF 病理生理学，帮助识别新的治疗靶点和生物标志物。最终，将空间转录组学整合到 MF 研究中有望提高诊断精度和治疗创新，解决这种疾病的多方面挑战。© 2024。作者。

Myelofibrosis (MF) is a complex myeloproliferative neoplasm characterized by abnormal hematopoietic stem cell proliferation and subsequent bone marrow (BM) fibrosis. First documented in the late 19th century, MF has since been extensively studied to unravel its pathophysiology, clinical phenotypes, and therapeutic interventions. MF can be classified into primary and secondary forms, both driven by mutations in genes such as JAK2, CALR, and MPL, which activate the JAK-STAT signaling pathway. These driver mutations are frequently accompanied by additional non-driver mutations in genes like TET2, SRSF2, and TP53, contributing to disease complexity. The BM microenvironment, consisting of stromal cells, extracellular matrix, and cytokines such as TGF-β and TNF-α, plays a critical role in fibrosis and aberrant hematopoiesis. Clinically, MF manifests with symptoms ranging from anemia, splenomegaly, and fatigue to severe complications such as leukemic transformation. Splenomegaly, caused by extramedullary hematopoiesis, leads to abdominal discomfort and early satiety. Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches. Allogeneic hematopoietic stem cell transplantation remains the only curative option, though it is limited to younger, high-risk patients. Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape. Spatially Resolved Transcriptomics (SRT) has revolutionized the study of gene expression within the spatial context of tissues, providing unprecedented insights into cellular heterogeneity, spatial gene regulation, and microenvironmental interactions, including stromal-hematopoietic dynamics. SRT enables high-resolution mapping of gene expression in the BM and spleen, revealing molecular signatures, spatial heterogeneity, and pathological niches that drive disease progression. These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease.© 2024. The Author(s).