骨髓增生异常综合征（MDS）包括起源于造血干细胞（HSCs）肿瘤变形的血液学疾病。然而，在MDS衍生的骨髓中区分HSCs和其肿瘤对应物仍具有挑战性。我们假设，在MDS患者中，具有免疫表型标记异常表达的未成熟CD34+CD38-细胞反映肿瘤干细胞，并且其频率能够预测白血病进展。我们分析了68名MDS患者和53名对照样本，并将HSCs与表现为膜异常的免疫表型异常HSCs（IA-HSCs）（CD7、CD11b、CD22、CD33、CD44、CD45RA、CD56、CD123、CD366或CD371）区分开来。三分之一的MDS骨髓（23/68）包含IA-HSCs。 IA-HSCs的存在与造血功能失调（细胞减少症旁边的不成比例扩展CD34+子集）以及白血病进展的危险性增加（HR = 25，95％CI：2.9-218）相关，这是独立于传统风险因素的。在2年的跟踪中，IA-HSCs的存在与预测白血病进展的敏感性和特异性分别为83％（95％CI：36-99％）和71％（95％CI：58-81％）。在一个选定的队列（n = 10）中，大多数带有IA-HSCs的MDS骨髓显示出基因组复杂性和高人类爆炸计数，与没有IA-HSCs的MDS骨髓形成对比。这项研究表明，MDS-BMs中IA-HSCs的存在预测白血病进展，表明IA-HSCs具有作为预后生物标志物的临床潜力。©2023.作者。

Myelodysplastic syndromes (MDS) comprise hematological disorders that originate from the neoplastic transformation of hematopoietic stem cells (HSCs). However, discrimination between HSCs and their neoplastic counterparts in MDS-derived bone marrows (MDS-BMs) remains challenging. We hypothesized that in MDS patients immature CD34+CD38- cells with aberrant expression of immunophenotypic markers reflect neoplastic stem cells and that their frequency predicts leukemic progression. We analyzed samples from 68 MDS patients and 53 controls and discriminated HSCs from immunophenotypic aberrant HSCs (IA-HSCs) expressing membrane aberrancies (CD7, CD11b, CD22, CD33, CD44, CD45RA, CD56, CD123, CD366 or CD371). One-third of the MDS-BMs (23/68) contained IA-HSCs. The presence of IA-HSCs correlated with perturbed hematopoiesis (disproportionally expanded CD34+ subsets beside cytopenias) and an increased hazard of leukemic progression (HR = 25, 95% CI: 2.9-218) that was independent of conventional risk factors. At 2 years follow-up, the sensitivity and specificity of presence of IA-HSCs for predicting leukemic progression was 83% (95% CI: 36-99%) and 71% (95% CI: 58-81%), respectively. In a selected cohort (n = 10), most MDS-BMs with IA-HSCs showed genomic complexity and high human blast counts following xenotransplantation into immunodeficient mice, contrasting MDS-BMs without IA-HSCs. This study demonstrates that the presence of IA-HSCs within MDS-BMs predicts leukemic progression, indicating the clinical potential of IA-HSCs as a prognostic biomarker.© 2023. The Author(s).