Crampe Mireille, Andrews Claire, Fortune Anne, Langabeer Stephen E
Cancer Molecular Diagnostics, St. James's Hospital, Dublin 8, Ireland.
Department of Haematology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
Case Rep Hematol. 2017;2017:3548936. doi: 10.1155/2017/3548936. Epub 2017 Dec 11.
The introduction of the tyrosine kinase inhibitor (TKI) imatinib has revolutionised the outlook of chronic myeloid leukemia (CML); however, a significant proportion of patients develop resistance through several mechanisms, of which acquisition of kinase domain mutations is prevalent. In chronic-phase patients, these mutations become evident early in the disease course. A case is described of a chronic-phase CML patient who achieved a sustained, deep molecular response but who developed an Y253H kinase domain mutation nearly nine years after commencing imatinib. Switching therapy to bosutinib resulted in a rapid reachievement of a major molecular response. Long-term TKI treatment impacts on quality of life and late losses of responses are usually due to lack of adherence. This case highlights the requirement for kinase domain mutation analysis in those CML patients on long-term imatinib who lost their molecular response, regardless of whether nonadherence is suspected.
酪氨酸激酶抑制剂（TKI）伊马替尼的引入彻底改变了慢性髓性白血病（CML）的治疗前景；然而，相当一部分患者会通过多种机制产生耐药性，其中激酶结构域突变的获得较为普遍。在慢性期患者中，这些突变在疾病进程早期就会显现出来。本文描述了一例慢性期CML患者，该患者在开始使用伊马替尼近九年后出现Y253H激酶结构域突变，此前已实现持续的深度分子反应。换用博舒替尼治疗后迅速再次达到主要分子反应。长期TKI治疗会影响生活质量，反应的后期丧失通常是由于依从性差。该病例强调，对于那些在长期接受伊马替尼治疗后失去分子反应的CML患者，无论是否怀疑存在依从性问题，都需要进行激酶结构域突变分析。
