Department of Hematology, Chongqing University FuLing Hospital, Chongqing, Central Laboratory, Chongqing University FuLing Hospital, Chongqing, China.
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
J Cell Mol Med. 2024 Feb;28(3):e18114. doi: 10.1111/jcmm.18114.
Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).
携带费城染色体样急性淋巴细胞白血病（Ph-like ALL）的患者往往预后不佳，该亚组中常检测到 PDGFRB 基因融合。我们的研究揭示了一种新的融合基因，TERF2::PDGFRB，并且我们发现携带这种融合基因的患者对达沙替尼敏感。携带 TERF2::PDGFRB 融合基因的 Ba/F3 细胞通过激活 p-PDGFRB 和 p-STAT5 信号通路，表现出对 IL-3 的非依赖性细胞增殖。这些细胞表现出减少的细胞凋亡，并在体外对伊马替尼敏感。当将这些细胞注入小鼠体内时，携带 TERF2::PDGFRB 融合基因的 Ba/F3 细胞在细胞衍生的移植物模型中诱导肿瘤发生和寿命缩短，但用伊马替尼治疗可以改善这种结果。总之，我们已经确定了新型的 TERF2::PDGFRB 融合基因，它在体外和体内均表现出致癌潜能，使其成为酪氨酸激酶抑制剂（TKI）的潜在治疗靶点。
