Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia.
Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia.
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DOI：
10.1155/2013/490740
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发表时间：
2013
影响因子：
0.7
通讯作者：
Langabeer SE
中科院分区：
文献类型：
--
作者：
McCarron SL;Maher K;Kelly J;Ryan MF;Langabeer SE
少数慢性粒细胞白血病（CML）患者表达的变体转录本中，e19 a2 BCR-ABL 1融合是最常见的。e19 a2 BCR-ABL 1 CML患者中酪氨酸激酶抑制剂（TKI）耐药的报道很少。本文描述了一例e19 a2 BCR-ABL 1 CML患者，在开始TKI治疗后不久，伊马替尼耐药（与Q252 H ABL 1激酶结构域突变相关）变得明显。患者迅速转化为骨髓原始细胞危象（BC），伴有严重骨髓纤维化，对第二代TKI无显著分子应答。合并症使临床病程复杂化，患者迅速死于晚期疾病。这种Q252 H相关TKI耐药伴快速BC转化的情况先前未在e19 a2 BCR-ABL 1 CML中记录。该病例强调了TKI耐药BC CML管理中存在的相当大的挑战，特别是在老年患者中。
A minority of chronic myeloid leukaemia (CML) patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI) resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC) with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.