Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.
Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.
复制标题
DOI：
10.1038/s41467-021-23097-w
复制
发表时间：
2021-05-14
影响因子：
16.6
通讯作者：
Shih LY
中科院分区：
文献类型：
--
作者：
Ochi Y;Yoshida K;Huang YJ;Kuo MC;Nannya Y;Sasaki K;Mitani K;Hosoya N;Hiramoto N;Ishikawa T;Branford S;Shanmuganathan N;Ohyashiki K;Takahashi N;Takaku T;Tsuchiya S;Kanemura N;Nakamura N;Ueda Y;Yoshihara S;Bera R;Shiozawa Y;Zhao L;Takeda J;Watatani Y;Okuda R;Makishima H;Shiraishi Y;Chiba K;Tanaka H;Sanada M;Takaori-Kondo A;Miyano S;Ogawa S;Shih LY
原始细胞危象(BC)预测慢性粒细胞白血病(CML)患者的悲惨结局。尽管额外的基因改变在卑诗省发挥了核心作用，但这些改变的景观和预后影响仍然难以捉摸。在这里，我们使用外显子组和靶向测序技术，全面研究了216例CML患者的136个BC期和148个慢性期(CP)样本的遗传异常。在136例BC患者中，126例(92.6%)发现一种或多种基因异常，包括RUNX1-ETS2融合和NBEAL2突变。在从CP到BC的转变过程中，基因改变的数量增加，这一变化显著地被酪氨酸激酶抑制剂(TKI)抑制。BC的谱系和TKI的先前使用与不同的分子图谱相关。值得注意的是，基因改变，而不是临床变量，有助于更好地预测BC的预后。总之，基因异常可以帮助预测临床结果，并指导慢性粒细胞白血病的临床决策。在慢性粒细胞白血病(CML)中，原始细胞危象和对酪氨酸激酶抑制剂耐药的驱动因素尚未完全确定。在这里，作者用基因组技术分析了一组CML样本，发现至少有一个驱动程序改变与疾病进展和更差的预后有关。
Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML. In chronic myeloid leukaemia (CML), the drivers of blast crisis and resistance to tyrosine kinase inhibitors are not fully characterised. Here, the authors analyse a cohort of CML samples with genomic technologies and find that at least one driver alteration is associated with progression and worse prognosis.
登录
查看更多内容
影响因子：
82.9
作者：
Bernard E;Nannya Y;Hasserjian RP;Devlin SM;Tuechler H;Medina-Martinez JS;Yoshizato T;Shiozawa Y;Saiki R;Malcovati L;Levine MF;Arango JE;Zhou Y;Solé F;Cargo CA;Haase D;Creignou M;Germing U;Zhang Y;Gundem G;Sarian A;van de Loosdrecht AA;Jädersten M;Tobiasson M;Kosmider O;Follo MY;Thol F;Pinheiro RF;Santini V;Kotsianidis I;Boultwood J;Santos FPS;Schanz J;Kasahara S;Ishikawa T;Tsurumi H;Takaori-Kondo A;Kiguchi T;Polprasert C;Bennett JM;Klimek VM;Savona MR;Belickova M;Ganster C;Palomo L;Sanz G;Ades L;Della Porta MG;Elias HK;Smith AG;Werner Y;Patel M;Viale A;Vanness K;Neuberg DS;Stevenson KE;Menghrajani K;Bolton KL;Fenaux P;Pellagatti A;Platzbecker U;Heuser M;Valent P;Chiba S;Miyazaki Y;Finelli C;Voso MT;Shih LY;Fontenay M;Jansen JH;Cervera J;Atsuta Y;Gattermann N;Ebert BL;Bejar R;Greenberg PL;Cazzola M;Hellström-Lindberg E;Ogawa S;Papaemmanuil E
通讯作者：
Papaemmanuil E
影响因子：
30.8
作者：
通讯作者：
--
酪氨酸激酶抑制剂治疗后慢性粒细胞白血病的体细胞突变动态谱
影响因子：
20.3
作者：
Kim, TaeHyung;Tyndel, Marc S.;Kim, Dennis (Dong Hwan)
通讯作者：
Kim, Dennis (Dong Hwan)
影响因子：
11.4
作者：
Ernst, Thomas;Busch, Melinda;Gruhn, Bernd
通讯作者：
Gruhn, Bernd
DOI：
10.1056/nejmoa1301689
发表时间：
2013-05-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Ley TJ;Miller C;Ding L;Raphael BJ;Mungall AJ;Robertson A;Hoadley K;Triche TJ Jr;Laird PW;Baty JD;Fulton LL;Fulton R;Heath SE;Kalicki-Veizer J;Kandoth C;Klco JM;Koboldt DC;Kanchi KL;Kulkarni S;Lamprecht TL;Larson DE;Lin L;Lu C;McLellan MD;McMichael JF;Payton J;Schmidt H;Spencer DH;Tomasson MH;Wallis JW;Wartman LD;Watson MA;Welch J;Wendl MC;Ally A;Balasundaram M;Birol I;Butterfield Y;Chiu R;Chu A;Chuah E;Chun HJ;Corbett R;Dhalla N;Guin R;He A;Hirst C;Hirst M;Holt RA;Jones S;Karsan A;Lee D;Li HI;Marra MA;Mayo M;Moore RA;Mungall K;Parker J;Pleasance E;Plettner P;Schein J;Stoll D;Swanson L;Tam A;Thiessen N;Varhol R;Wye N;Zhao Y;Gabriel S;Getz G;Sougnez C;Zou L;Leiserson MD;Vandin F;Wu HT;Applebaum F;Baylin SB;Akbani R;Broom BM;Chen K;Motter TC;Nguyen K;Weinstein JN;Zhang N;Ferguson ML;Adams C;Black A;Bowen J;Gastier-Foster J;Grossman T;Lichtenberg T;Wise L;Davidsen T;Demchok JA;Shaw KR;Sheth M;Sofia HJ;Yang L;Downing JR;Eley G
通讯作者：
Eley G