Molica Matteo, Abruzzese Elisabetta, Breccia Massimo
Haematology Unit, S. Eugenio Hospital, Rome, Italy.
Tor Vergata University Hospital, Department of Hematology, Rome, Italy.
Mediterr J Hematol Infect Dis. 2020 Sep 1;12(1):e2020062. doi: 10.4084/MJHID.2020.062. eCollection 2020.
Chronic myeloid leukemia (CML) is characterized by the presence of the fusion gene. In more than 95% of CML patients, the typical transcript subtypes are e13a2 (b2a2), e14a2 (b3a2), or the simultaneous expression of both. Other less frequent transcript subtypes, such as e1a2, e2a2, e6a2, e19a2, e1a3, e13a3, and e14a3, have been sporadically reported. The main purpose of this review is to assess the possible impact of different transcripts on the response rate to tyrosine kinase inhibitors (TKIs), the achievement of stable deep molecular responses (s-DMR), the potential maintenance of treatment-free remission (TFR), and long-term outcome of CML patients treated with TKIs. According to the majority of published studies, patients with e13a2 transcript treated with imatinib have lower and slower cytogenetic and molecular responses than those with e14a2 transcript. They should be considered a high-risk group that would most benefit from frontline treatment with second-generation TKIs (2GTIKIs). Although few studies have been published, similar significant differences in response rates to 2GTKIs have been not reported. The e14a2 transcript seems to be a favorable prognostic factor for obtaining s-DMR, irrespective of the TKI received, and is also associated with a very high rate of TFR maintenance. Indeed, patients with e13a2 transcript achieve a lower rate of s-DMR and experience a higher probability of TFR failure. According to most reported data in the literature, the type of transcript does not seem to affect long-term outcomes of CML patients treated with TKIs. In TFR, the e14a2 transcript appears to be related to favorable responses. 2GTKIs as frontline therapy might be a convenient approach in patients with e13a2 transcript to achieve optimal long-term outcomes.
慢性髓性白血病（CML）的特征是存在融合基因。在超过95%的CML患者中，典型的转录本亚型是e13a2（b2a2）、e14a2（b3a2），或两者同时表达。其他不太常见的转录本亚型，如e1a2、e2a2、e6a2、e19a2、e1a3、e13a3和e14a3，也有零星报道。本综述的主要目的是评估不同转录本对酪氨酸激酶抑制剂（TKIs）治疗反应率、稳定深度分子反应（s-DMR）的实现、无治疗缓解（TFR）的潜在维持以及接受TKIs治疗的CML患者长期预后的可能影响。根据大多数已发表的研究，接受伊马替尼治疗的e13a2转录本患者的细胞遗传学和分子反应比e14a2转录本患者更低、更慢。他们应被视为最能从第二代TKIs（2GTKIs）一线治疗中获益的高危人群。尽管发表的研究较少，但尚未报道对2GTKIs的反应率有类似的显著差异。无论接受何种TKI，e14a2转录本似乎是获得s-DMR的有利预后因素，并且也与非常高的TFR维持率相关。事实上，e13a2转录本患者的s-DMR率较低，TFR失败的可能性较高。根据文献中大多数报道的数据，转录本类型似乎不影响接受TKIs治疗的CML患者的长期预后。在TFR方面，e14a2转录本似乎与良好反应相关。2GTKIs作为一线治疗可能是一种方便的方法，可使e13a2转录本患者实现最佳长期预后。
