High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults
High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults
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DOI：
10.1200/jco.2016.69.0073
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发表时间：
2017-02-01
影响因子：
45.3
通讯作者：
Mullighan, Charles G.
中科院分区：
文献类型：
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作者：
Roberts, Kathryn G.;Gu, Zhaohui;Mullighan, Charles G.
目的费城染色体（Ph）样急性淋巴细胞白血病（ALL）是儿童ALL的一种高危亚型，其特征是激酶激活改变，可用酪氨酸激酶抑制剂治疗。我们试图定义的患病率和基因组景观的Ph-样ALL在成人和评估响应常规chemotherapy.Patients和MethodsThe Ph-样ALL的频率进行了评估的798例B细胞ALL年龄21至86岁的基因表达谱。确定Ph样ALL与非Ph样ALL患者的无事件生存期和总生存期。详细的基因组分析进行了180 194例Ph样ALL。结果Ph样ALL患者占成人ALL的20%以上，包括27.9%的年轻人（年龄21至39岁），20.4%的成人（年龄40至59岁），24.0%的老年人（年龄60至86岁）。总体而言，Ph样ALL患者的5年无事件生存率低于非Ph样ALL患者（分别为22.5% [95% CI，14.9%至29.3%; n = 155] vs 49.3% [95% CI，42.8%至56.2%; n = 247]; P <0.001）。我们在88%的Ph样ALL患者中发现了激酶激活改变，包括CRLF 2重排（51%）、ABL类融合（9.8%）、JAK 2或EPOR重排（12.4%）、其他JAK-STAT序列突变（7.2%）、其他激酶改变（4.1%）和Ras通路突变（3.6%）。11个新的激酶重排被确定，包括4个涉及新的激酶或细胞因子受体基因和7个涉及新的合作伙伴，以前确定的genes. ConclusionPh样ALL是一个高度流行的亚型ALL在成人和不良后果。在Ph样ALL中，激酶激活改变的多样性具有重要的治疗意义。需要进行将酪氨酸激酶抑制剂与常规治疗进行比较的试验，以评估这些药物在治疗Ph样ALL中的临床效用。(C)2016年美国临床肿瘤学会
PurposePhiladelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy.Patients and MethodsThe frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL.ResultsPatients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes.ConclusionPh-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL. (C) 2016 by American Society of Clinical Oncology