文章：

日本儿童费城染色体阴性B细胞前体急性淋巴细胞白血病伴激酶融合的特征研究

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

原文发布日期：2016-05-13

DOI: 10.1038/bcj.2016.28

类型: Original Article

开放获取: 是

英文摘要：

Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase–PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/μl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.

摘要翻译： 

近期研究表明，在高风险B细胞前体急性淋巴细胞白血病（BCP-ALL）患者中，存在相当大比例患者携带涉及酪氨酸激酶和细胞因子受体的融合基因（如ABL1、PDGFRB、JAK2和CRLF2），这些靶点可通过酪氨酸激酶抑制剂（TKIs）进行干预。本研究通过对373例无常见遗传学异常的BCP-ALL患者进行转录组分析或多重逆转录PCR分析，发现29例患者存在激酶融合基因。临床特征显示：男性居多（男女比22:7）、发病年龄较大（平均8.8岁）、诊断时高白细胞计数（平均94,200/μl），体现了美国国家癌症研究所高风险（NCI-HR）患者的主导地位（标危/高危比为8:21）。基因分析鉴定出3例ABL1重排、8例PDGFRB重排、2例JAK2重排、3例IgH-EPOR融合及1例NCOR1-LYN融合。在14例CRLF2重排患者中，有2例同时存在IgH-EPOR和PDGFRB重排。22例患者中16例存在IKZF1缺失。5年无事件生存率和总生存率分别为48.6±9.7%和73.5±8.6%。若未采用基于微小残留病的精准分层治疗，临床结局并不理想。此外，需要进一步评估在该队列中联合使用TKIs与常规化疗（无需异基因造血干细胞移植）的疗效。

原文链接：

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan