Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.
Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.
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DOI：
10.1038/ng.2558
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发表时间：
2013-03
期刊：
影响因子：
30.8
通讯作者：
Carroll, William L.
中科院分区：
文献类型：
--
作者：
Meyer, Julia A.;Wang, Jinhua;Hogan, Laura E.;Yang, Jun J.;Dandekar, Smita;Patel, Jay P.;Tang, Zuojian;Zumbo, Paul;Li, Sheng;Zavadil, Jiri;Levine, Ross L.;Cardozo, Timothy;Hunger, Stephen P.;Raetz, Elizabeth A.;Evans, William E.;Morrison, Debra J.;Mason, Christopher E.;Carroll, William L.
复发性儿童急性淋巴细胞白血病（ALL）由于内在耐药性，尽管进行了强化再治疗，但预后不良。介导耐药性的生物学途径尚不清楚。在这里，我们报告的转录组配置文件匹配的诊断和复发的骨髓标本，从10名儿童B淋巴细胞白血病患者使用RNA测序。转录组测序发现了20个新获得的、在初步诊断时不存在的新型非同义突变，其中两名患者在同一基因（5 '-核苷酸酶NT 5C 2）中携带复发特异性突变。在另外61份复发标本中完成了NT 5C 2的全外显子测序，确定了另外5例病例。突变蛋白的酶促分析显示，碱基取代赋予增加的酶活性和对核苷类似物治疗的抗性。临床上，所有携带NT 5C 2突变的患者早期复发，或在初次诊断后36个月内复发（p=0.03）。这些结果表明，NT 5C 2的突变与ALL中耐药克隆的生长有关。
Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis despite intensive retreatment, due to intrinsic drug resistance. The biological pathways that mediate resistance are unknown. Here we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten pediatric B lymphoblastic leukemia patients using RNA-sequencing. Transcriptome sequencing identified 20 newly acquired novel non-synonymous mutations not present at initial diagnosis, of which two patients harbored relapse specific mutations in the same gene, NT5C2, a 5′-nucleotidase. Full exon sequencing of NT5C2 was completed in 61 additional relapse specimens, identifying five additional cases. Enzymatic analysis of mutant proteins revealed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analogue therapies. Clinically, all patients who harbored NT5C2 mutations relapsed early, or within 36 months of initial diagnosis (p=0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug resistant clones in ALL.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Eapen, M;Raetz, E;Davies, SM
通讯作者：
Davies, SM
影响因子：
5.8
作者：
Jordheim, Lars Petter;Marton, Zsuzsanna;Chaloin, Laurent
通讯作者：
Chaloin, Laurent
DOI：
10.1046/j.1432-1327.1999.00099.x
发表时间：
1999-02-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Spychala, J;Chen, V;Mitchell, BS
通讯作者：
Mitchell, BS