The genomic landscape of hypodiploid acute lymphoblastic leukemia.
The genomic landscape of hypodiploid acute lymphoblastic leukemia.
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DOI：
10.1038/ng.2532
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发表时间：
2013-03
期刊：
影响因子：
30.8
通讯作者：
Mullighan, Charles G.
中科院分区：
文献类型：
--
作者：
Holmfeldt, Linda;Wei, Lei;Diaz-Flores, Ernesto;Walsh, Michael;Zhang, Jinghui;Ding, Li;Payne-Turner, Debbie;Churchman, Michelle;Andersson, Anna;Chen, Shann-Ching;McCastlain, Kelly;Becksfort, Jared;Ma, Jing;Wu, Gang;Patel, Samir N.;Heatley, Susan L.;Phillips, Letha A.;Song, Guangchun;Easton, John;Parker, Matthew;Chen, Xiang;Rusch, Michael;Boggs, Kristy;Vadodaria, Bhavin;Hedlund, Erin;Drenberg, Christina;Baker, Sharyn;Pei, Deqing;Cheng, Cheng;Huether, Robert;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda L.;Tabib, Yashodhan;Dooling, David J.;Ochoa, Kerri;Minden, Mark;Lewis, Ian D.;To, L. Bik;Marlton, Paula;Roberts, Andrew W.;Raca, Gordana;Stock, Wendy;Neale, Geoffrey;Drexler, Hans G.;Dickins, Ross A.;Ellison, David W.;Shurtleff, Sheila A.;Pui, Ching-Hon;Ribeiro, Raul C.;Devidas, Meenakshi;Carroll, Andrew J.;Heerema, Nyla A.;Wood, Brent;Borowitz, Michael J.;Gastier-Foster, Julie M.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Hunger, Stephen P.;Loh, Mignon L.;Mullighan, Charles G.
亚二倍体急性淋巴细胞白血病（ALL）是ALL的一种亚型，以非整倍体和不良预后为特征，其遗传基础尚不清楚。124例亚二倍体ALL病例的基因组分析，包括40例病例的全基因组和外显子组测序，确定了两种亚型，其在非整倍体、转录谱和亚显微遗传改变的严重程度上不同。具有24-31条染色体的近单倍体病例具有靶向受体酪氨酸激酶和Ras信号传导（71%）和淋巴转录因子IKZF 3（AIOLOS; 13%）的改变。相比之下，具有32-39条染色体的低亚二倍体ALL的特征在于TP 53改变（91.2%），其通常存在于非肿瘤细胞中，以及IKZF 2（HELIOS; 53%）和RB 1（41%）的改变。近单倍体和低亚二倍体肿瘤均表现出Ras和PI 3 K信号通路的激活，并且对PI 3 K抑制剂敏感，这表明这些药物应被探索作为这种侵袭性白血病形式的新治疗策略。
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole genome and exome sequencing of 40 cases, identified two subtypes that differ in severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24–31 chromosomes harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and the lymphoid transcription factor IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL with 32–39 chromosomes are characterized by TP53 alterations (91.2%) which are commonly present in non-tumor cells, and alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras- and PI3K signaling pathways, and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
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作者：
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作者：
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通讯作者：
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