Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, Amsterdam, The Netherlands.
Blood Adv. 2021 Sep 28;5(18):3726-3735. doi: 10.1182/bloodadvances.2021004845.
Myeloid dysplastic syndrome (MDS) reflects a preleukemic bone marrow (BM) disorder with limited treatment options and poor disease survival. As only a minority of MDS patients are eligible for curative hematopoietic stem cell transplantation, there is an urgent need to develop alternative treatment options. Chronic activation of Wnt/β-catenin has been implicated to underlie MDS formation and recently assigned to drive MDS transformation to acute myeloid leukemia. Wnt/β-catenin signaling therefore may harbor a pharmaceutical target to treat MDS and/or prevent leukemia formation. However, targeting the Wnt/β-catenin pathway will also affect healthy hematopoiesis in MDS patients. The control of Wnt/β-catenin in healthy hematopoiesis is poorly understood. Whereas Wnt/β-catenin is dispensable for steady-state erythropoiesis, its activity is essential for stress erythropoiesis in response to BM injury and anemia. Manipulation of Wnt/β-catenin signaling in MDS may therefore deregulate stress erythropoiesis and even increase anemia severity. Here, we provide a comprehensive overview of the most recent and established insights in the field to acquire more insight into the control of Wnt/β-catenin signaling in healthy and inefficient erythropoiesis as seen in MDS.
骨髓增生异常综合征 (MDS) 反映了一种骨髓前白血病障碍，其治疗选择有限，疾病生存状况较差。由于只有少数 MDS 患者有资格接受根治性造血干细胞移植，因此迫切需要开发替代治疗方案。Wnt/β-catenin 的慢性激活被认为是 MDS 形成的基础，并最近被认为可驱动 MDS 向急性髓系白血病转化。因此，Wnt/β-catenin 信号通路可能具有治疗 MDS 和/或预防白血病形成的药物靶点。然而，靶向 Wnt/β-catenin 通路也会影响 MDS 患者的健康造血。Wnt/β-catenin 在健康造血中的控制作用了解甚少。虽然 Wnt/β-catenin 对稳态红细胞生成是可有可无的，但它的活性对于应对 BM 损伤和贫血的应激红细胞生成是必不可少的。因此，在 MDS 中操纵 Wnt/β-catenin 信号可能会使应激红细胞生成失调，甚至加重贫血严重程度。在这里，我们全面概述了该领域最新和已确立的见解，以更深入地了解健康和 MDS 中低效红细胞生成中 Wnt/β-catenin 信号的控制。
