Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
St Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Blood. 2021 Dec 9;138(23):2347-2359. doi: 10.1182/blood.2021010980.
The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.
转录因子信号转导子和转录激活子 5A（STAT5A）和 STAT5B 在造血和白血病中至关重要。它们被广泛认为具有冗余功能，但我们描述了 STAT5B 在驱动造血和白血病干细胞（HSCs/LSCs）自我更新中的独特作用。我们发现 STAT5B 在 HSCs 和 LSCs 中特异性激活，在那里它诱导许多与静止和自我更新相关的基因，包括表面标记物 CD9。CD9 水平代表 STAT5 驱动的白血病患者的预后标志物，我们的研究结果表明，抗 CD9 抗体可能在治疗中有用，以靶向和消除 LSCs。我们表明，在正常和恶性造血中，将 STAT5A 和 STAT5B 视为不同实体是至关重要的。
