The genomic landscape of juvenile myelomonocytic leukemia.
The genomic landscape of juvenile myelomonocytic leukemia.
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DOI：
10.1038/ng.3400
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发表时间：
2015-11
期刊：
影响因子：
30.8
通讯作者：
Loh ML
中科院分区：
文献类型：
--
作者：
Stieglitz E;Taylor-Weiner AN;Chang TY;Gelston LC;Wang YD;Mazor T;Esquivel E;Yu A;Seepo S;Olsen S;Rosenberg M;Archambeault SL;Abusin G;Beckman K;Brown PA;Briones M;Carcamo B;Cooper T;Dahl GV;Emanuel PD;Fluchel MN;Goyal RK;Hayashi RJ;Hitzler J;Hugge C;Liu YL;Messinger YH;Mahoney DH Jr;Monteleone P;Nemecek ER;Roehrs PA;Schore RJ;Stine KC;Takemoto CM;Toretsky JA;Costello JF;Olshen AB;Stewart C;Li Y;Ma J;Gerbing RB;Alonzo TA;Getz G;Gruber T;Golub T;Stegmaier K;Loh ML
青少年粒单核细胞白血病（JMML）是一种预后不良的儿童骨髓增生性肿瘤（MPN）。NF 1、NRAS、KRAS、PTPN 11和CBL突变发生在85%的患者中，但目前还没有风险分层算法能够预测哪些患者对常规治疗难治，从而成为实验性治疗的候选者。此外，除了Ras/MAPK途径之外，很少有其他分子途径被鉴定为这种新的治疗策略的基础。因此，我们试图从诊断到复发和转化为急性髓性白血病的患者的系列样本的基因组特征，以扩大我们对JMML突变谱的了解。我们确定了参与信号转导、基因剪接、多梳抑制复合物2（PRC 2）和转录的基因中的复发性突变。重要的是，诊断时存在的体细胞改变的数量似乎是结果的主要决定因素。
Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.