Wang Xiaoou, Li Zhenggang, Shen Jing, Liu Lin
Department of Hematology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Cell Biol Toxicol. 2024 Dec 21;41(1):11. doi: 10.1007/s10565-024-09965-3.
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid progenitor cells. Despite advancements in treatment, the prognosis for AML patients remains poor, highlighting the need for novel therapeutic targets. Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6), also known as SHP-1, is a critical regulator of hematopoietic cell signaling and has been implicated in various leukemias. This study investigates the therapeutic potential of targeting PTPN6 in AML. We employed both in vitro and in vivo models to evaluate the effects of PTPN6 inhibition on AML cell proliferation, apoptosis, and differentiation. Our results demonstrate that PTPN6 inhibition leads to a significant reduction in AML cell viability, induces apoptosis, and promotes differentiation of leukemic cells into mature myeloid cells. Mechanistic studies revealed that PTPN6 inhibition disrupts key signaling pathways involved in AML pathogenesis, including the JAK/STAT and PI3K/AKT pathways. Furthermore, the combination of PTPN6 inhibitors with standard chemotherapeutic agents exhibited a synergistic effect, enhancing the overall therapeutic efficacy. These findings suggest that PTPN6 is a promising therapeutic target in AML and warrants further investigation into the development of PTPN6 inhibitors for clinical application in AML treatment.
急性髓系白血病（AML）是一种异质性血液系统恶性肿瘤，其特征为髓系祖细胞的克隆性扩增。尽管治疗取得了进展，但AML患者的预后仍然很差，这凸显了对新型治疗靶点的需求。蛋白酪氨酸磷酸酶非受体6型（PTPN6），也称为SHP-1，是造血细胞信号传导的关键调节因子，并且与多种白血病有关。本研究调查了靶向PTPN6在AML中的治疗潜力。我们采用体外和体内模型来评估PTPN6抑制对AML细胞增殖、凋亡和分化的影响。我们的结果表明，PTPN6抑制导致AML细胞活力显著降低，诱导凋亡，并促进白血病细胞分化为成熟髓系细胞。机制研究表明，PTPN6抑制破坏了AML发病机制中涉及的关键信号通路，包括JAK/STAT和PI3K/AKT通路。此外，PTPN6抑制剂与标准化疗药物联合使用表现出协同作用，增强了总体治疗效果。这些发现表明，PTPN6是AML中一个有前景的治疗靶点，值得进一步研究开发PTPN6抑制剂用于AML治疗的临床应用。
