An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.
An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.
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DOI：
10.1016/j.ccr.2012.10.007
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发表时间：
2012-11-13
期刊：
影响因子：
50.3
通讯作者：
Downing JR
中科院分区：
文献类型：
--
作者：
Gruber TA;Larson Gedman A;Zhang J;Koss CS;Marada S;Ta HQ;Chen SC;Su X;Ogden SK;Dang J;Wu G;Gupta V;Andersson AK;Pounds S;Shi L;Easton J;Barbato MI;Mulder HL;Manne J;Wang J;Rusch M;Ranade S;Ganti R;Parker M;Ma J;Radtke I;Ding L;Cazzaniga G;Biondi A;Kornblau SM;Ravandi F;Kantarjian H;Nimer SD;Döhner K;Döhner H;Ley TJ;Ballerini P;Shurtleff S;Tomizawa D;Adachi S;Hayashi Y;Tawa A;Shih LY;Liang DC;Rubnitz JE;Pui CH;Mardis ER;Wilson RK;Downing JR
为了确定非唐氏综合征急性巨核细胞白血病（non-DS-AMKL）的突变谱，我们对14例儿科患者的诊断性原始细胞进行了转录组测序，并在由34例儿科和28例成人AMKL白血病样本组成的复发/验证队列中验证了我们的发现。我们的分析在27%的儿科病例中发现了一个隐藏的16号染色体倒位[inv（16）（p13.3q24.3）]，它编码CBFA 2 T3-GLIS 2融合蛋白。CBFA 2 T3-GLIS 2在果蝇和小鼠造血细胞中的表达诱导了骨形态发生蛋白（BMP）信号传导，并导致造血祖细胞自我更新能力的显著增加。这些数据表明，CBFA 2 T3-GLIS 2的表达直接有助于白血病的发生。
To define the mutation spectrum in non-Down syndrome acute megkaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL leukemia samples. Our analysis identified a cryptic chromosome 16 inversion [inv(16)(p13.3q24.3)] in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling, and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.
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