慢性粒细胞白血病（CML）是一种骨髓增生性肿瘤，年发病率为2例/100 000，约占成人新诊断白血病病例的15%。CML的特点是平衡基因易位，t(9;22 ) (q34;q11.2)，涉及来自染色体 9q34 的 Abelson 鼠白血病 (ABL1) 基因与染色体 22q11.2 上的断点簇区域 (BCR) 基因的融合。这种重排被称为费城染色体。这种易位的分子结果是产生 BCR::ABL1 融合癌基因，该基因又转化为 BCR::ABL1 癌蛋白。 四种酪氨酸激酶抑制剂 (TKI)：伊马替尼、达沙替尼、博舒替尼和尼洛替尼已获得 FDA 批准。美国食品和药物管理局 (FDA) 用于新诊断的慢性期慢性粒细胞白血病 (CML-CP) 的一线治疗。在一线 CML-CP 治疗中使用第二代和第三代 TKI 的临床试验报告显示显着更深入和更快的反应，但对延长生存期没有影响，可能是因为它们具有强大的功效，并且对于细胞遗传学复发的患者可以使用有效的 TKI 挽救疗法一线 TKI 治疗。如果治疗的目的是提高生存率，则所有四种 TKI 都是等效的。对于患有高风险疾病且治疗目的是诱导无治疗缓解状态的年轻患者，第二代 TKI 可能更受青睐。对于一线治疗失败后的 CML，二线选择包括第二和第三-一代 TKI。虽然这些 TKI 有效且具有选择性，但针对不同患者和疾病特征（例如患者的合并症和财务状况、疾病阶段和 BCR::ABL1 突变状态）表现出独特的药理学特征和反应模式。发生 T315I“看门人”突变的患者对除 ponatinib、asciminib 和 olverembatinib 之外的所有现有 TKI 均表现出耐药性。对于患有 CML-CP 且至少两种 TKI 失败（由于耐药）的患者以及所有处于疾病晚期的患者，同种异体干细胞移植仍然是一种重要的治疗选择。所有 TKI 失败后出现细胞遗传学复发的老年患者，如果继续每日最有效/毒性最小的 TKI，并添加或不添加非 TKI 抗 CML 药物（羟基脲、奥马西他辛、阿扎胞苷），则可以维持长期生存。 、地西他滨、阿糖胞苷等）。© 2024 Wiley periodicals LLC。

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein.Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored.For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).© 2024 Wiley Periodicals LLC.