Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.
Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.
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DOI：
10.1038/s41467-018-03170-7
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发表时间：
2018-02-20
影响因子：
16.6
通讯作者：
Peifer M
中科院分区：
文献类型：
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作者：
Herling CD;Abedpour N;Weiss J;Schmitt A;Jachimowicz RD;Merkel O;Cartolano M;Oberbeck S;Mayer P;Berg V;Thomalla D;Kutsch N;Stiefelhagen M;Cramer P;Wendtner CM;Persigehl T;Saleh A;Altmüller J;Nürnberg P;Pallasch C;Achter V;Lang U;Eichhorst B;Castiglione R;Schäfer SC;Büttner R;Kreuzer KA;Reinhardt HC;Hallek M;Frenzel LP;Peifer M
破译癌细胞在治疗压力下的进化是理解导致治疗抵抗的机制的关键一步。为此，我们分析了 8 名慢性淋巴细胞白血病 (CLL) 患者的全外显子组测序数据，这些患者对 Venetoclax 的 BCL2 抑制产生了耐药性。在这里，我们报告了治疗期间发生的 BTG1（2 名患者）的复发突变和影响 CDKN2A/B（3 名患者）的纯合缺失，以及 BRAF 的突变和 CD274 (PD-L1) 的高水平局灶性扩增，这些可能精确定位分子畸变，为进一步的治疗干预提供结构。 BCL2 抑制剂维奈托克用于治疗复发/难治性慢性淋巴细胞白血病 (CLL)。在这里，作者通过对 8 名接受 Venetoclax 治疗的 CLL 患者进行全外显子组测序，展示了 Venetoclax 耐药性的克隆动态。
Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions. BCL2-inhibitor venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (CLL). Here, the authors show the clonal dynamics towards venetoclax resistance by performing whole-exome sequencing of 8 CLL patients undergoing venetoclax treatment.
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DOI：
10.1056/nejmoa1513257
发表时间：
2016-01-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Roberts AW;Davids MS;Pagel JM;Kahl BS;Puvvada SD;Gerecitano JF;Kipps TJ;Anderson MA;Brown JR;Gressick L;Wong S;Dunbar M;Zhu M;Desai MB;Cerri E;Heitner Enschede S;Humerickhouse RA;Wierda WG;Seymour JF
通讯作者：
Seymour JF
影响因子：
--
作者：
Quentmeier H;Pommerenke C;Ammerpohl O;Geffers R;Hauer V;MacLeod RA;Nagel S;Romani J;Rosati E;Rosén A;Uphoff CC;Zaborski M;Drexler HG
通讯作者：
Drexler HG
影响因子：
3.7
作者：
Budczies, Jan;Bockmayr, Michael;Stenzinger, Albrecht
通讯作者：
Stenzinger, Albrecht
影响因子：
64.8
作者：
Puente, Xose S.;Bea, Silvia;Campo, Elias
通讯作者：
Campo, Elias
影响因子：
64.5
作者：
Nik-Zainal S;Van Loo P;Wedge DC;Alexandrov LB;Greenman CD;Lau KW;Raine K;Jones D;Marshall J;Ramakrishna M;Shlien A;Cooke SL;Hinton J;Menzies A;Stebbings LA;Leroy C;Jia M;Rance R;Mudie LJ;Gamble SJ;Stephens PJ;McLaren S;Tarpey PS;Papaemmanuil E;Davies HR;Varela I;McBride DJ;Bignell GR;Leung K;Butler AP;Teague JW;Martin S;Jönsson G;Mariani O;Boyault S;Miron P;Fatima A;Langerød A;Aparicio SA;Tutt A;Sieuwerts AM;Borg Å;Thomas G;Salomon AV;Richardson AL;Børresen-Dale AL;Futreal PA;Stratton MR;Campbell PJ;Breast Cancer Working Group of the International Cancer Genome Consortium
通讯作者：
Breast Cancer Working Group of the International Cancer Genome Consortium