From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia.

This alteration gives rise to the BCR::ABL1 fusion oncogene, whose constitutive tyrosine kinase activity promotes uncontrolled proliferation and survival of leukemic cells.

这种改变导致了BCR::ABL1融合癌基因的产生，其持续的酪氨酸激酶活性促进了白血病细胞的无控制增殖和存活。

The discovery of this molecular driver laid the foundation for the development of tyrosine kinase inhibitors (TKIs), which transformed CML management from treatment with non-specific modalities to establishing a new paradigm for precision oncology with targeted therapies.

这一分子驱动因素的发现奠定了酪氨酸激酶抑制剂（TKIs）发展的基础，将慢性髓性白血病（CML）的管理从非特异性治疗转变为精准肿瘤学中靶向治疗的新范式。

Imatinib, the first TKI, demonstrated unprecedented hematologic, cytogenetic, and molecular responses, rapidly becoming the standard of care in CML.

首个TKI伊马替尼展示了前所未有的血液学、细胞遗传学和分子反应，迅速成为CML的标准治疗方法。

Subsequent generations of TKIs were developed to overcome resistance and intolerance to imatinib.

随后开发的酪氨酸激酶抑制剂（TKIs）旨在克服对伊马替尼的耐药性和不耐受。

These advances improved survival in CML, bringing life expectancy close to that of the general population for the patients who respond to treatment, and shifting treatment goals towards quality of life and the possibility of treatment-free remission (TFR).

这些进步改善了慢性髓性白血病（CML）患者的生存率，使对治疗有反应的患者的预期寿命接近一般人群，并将治疗目标转向生活质量以及实现无治疗缓解（TFR）的可能性。

Landmark discontinuation studies showed that approximately half of eligible patients can maintain TFR.

具有里程碑意义的停药研究显示，大约一半符合条件的患者可以维持治疗反应期（TFR）

Despite these achievements, important challenges remain, including TKI resistance, safety considerations, and the relatively low proportion of patients who achieve and maintain TFR.

尽管取得了这些成就，但仍面临重大挑战，包括酪氨酸激酶抑制剂（TKI）耐药、安全性考量以及实现并维持治疗反应期（TFR）的患者比例相对较低。

Newer-generation TKIs, combination strategies, immunomodulatory approaches, and emerging treatment modalities such as degraders offer promising avenues to further improve outcomes, expand TFR eligibility, ensure optimal quality of life, address resistance mechanisms, and render therapy available and affordable to all patients with CML worldwide.

新一代酪氨酸激酶抑制剂（TKIs）、联合治疗策略、免疫调节方法以及新兴的治疗方式，如降解剂，为改善治疗结果、扩大TFR（治疗无事件生存）适用范围、确保最佳生活质量、解决耐药机制以及使所有慢性髓性白血病（CML）患者都能获得可负担的治疗提供了有希望的途径。