Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No. 1, Changde Street, Zhongzheng District 10048, Taipei, Taiwan.
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA.
Sci Rep. 2021 Mar 11;11(1):5802. doi: 10.1038/s41598-021-85213-6.
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.
费城染色体样（Ph-like）急性淋巴细胞白血病（ALL）是一种高风险亚型，其特征是基因组改变激活细胞因子受体和激酶信号，与大多数儿童 ALL 临床试验中的不良结局相关。Ph-like ALL 患者中有一半存在激酶重排或融合。我们使用 212 例新诊断的儿童 B 细胞 ALL 回顾性队列研究了这些融合的频率和谱。没有已知染色体改变的样本采用多重逆转录聚合酶链反应（PCR）来鉴定已知的 Ph-like 激酶融合。对没有已知激酶融合的样本进行免疫球蛋白重链基因座（IGH）捕获和激酶捕获。我们在 212 例患者中的 5 例中检测到已知的激酶融合，包括 EBF1-PDGFRB、ETV6-ABL1、ZC3HAV1-ABL2、EPOR-IGH 和 CNTRL-ABL1。还鉴定出了 2 例 P2RY8-CRLF2 患者。与具有其他常见遗传改变的患者相比，具有非 Ph 激酶融合的患者 5 年无事件生存率和总生存率较低。我们的台湾队列中非 Ph 激酶融合的患病率低于白种人群报告的患病率。由于激酶融合的 B 细胞 ALL 结局较差，未来可能需要在台湾开展酪氨酸激酶抑制剂的临床试验。
