Yin Xiufeng, Li Xia, Jiang Hao, Lin Xiangjie, Ma Zhixin, Chen Xiaochang, Teng Qibei, Zhang Jin, Jin Jie
Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, P R China.
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P R China.
J Cancer. 2024 Mar 4;15(8):2424-2430. doi: 10.7150/jca.92202. eCollection 2024.
Cofilin (CFL1) is one critical member of the actin deploy family (ADF). Overexpression of CFL1 is associated with aggressive features and poor prognosis in malignancies. We evaluated the expression of CFL1 in patients with chronic myeloid leukemia in the chronic phase (CML-CP), acute myelocytic leukemia (AML) and healthy controls. The role of CFL1 in imatinib therapy was also investigated using cell line. We found that the expression of CFL1 was lower in CML patients than that in healthy controls, and was significantly upregulated after imatinib therapy (p<0.05). CML patients with lower CFL1 achieved higher Major molecular response (MMR) rate after 6 months of imatinib therapy (p<0.05). Cofilin, P-cofilin and F-actin, especially branched F-actin were all upregulated after imatinib therapy. The lower CFL1 expression before treatment may predicts a better response to imatinib. Imatinib affects F-actin remodeling in CML patients by regulating CFL1 expression and activity.
丝切蛋白（CFL1）是肌动蛋白解聚因子（ADF）家族的一个关键成员。CFL1的过表达与恶性肿瘤的侵袭性特征和不良预后相关。我们评估了慢性期慢性髓性白血病（CML-CP）、急性髓细胞白血病（AML）患者及健康对照中CFL1的表达情况。还使用细胞系研究了CFL1在伊马替尼治疗中的作用。我们发现，CML患者中CFL1的表达低于健康对照，且在伊马替尼治疗后显著上调（p<0.05）。CFL1水平较低的CML患者在伊马替尼治疗6个月后达到更高的主要分子反应（MMR）率（p<0.05）。伊马替尼治疗后，丝切蛋白、磷酸化丝切蛋白和丝状肌动蛋白，尤其是分支状丝状肌动蛋白均上调。治疗前CFL1表达较低可能预示对伊马替尼有更好的反应。伊马替尼通过调节CFL1的表达和活性影响CML患者的丝状肌动蛋白重塑。
