Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia.
Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia.
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DOI：
10.3324/haematol.2017.166215
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发表时间：
2017-08
期刊：
影响因子：
10.1
通讯作者：
Bloomfield CD
中科院分区：
文献类型：
--
作者：
Papaioannou D;Nicolet D;Volinia S;Mrózek K;Yan P;Bundschuh R;Carroll AJ;Kohlschmidt J;Blum W;Powell BL;Uy GL;Kolitz JE;Wang ES;Eisfeld AK;Orwick SJ;Lucas DM;Caligiuri MA;Stone RM;Byrd JC;Garzon R;Bloomfield CD
长链非编码核糖核酸（RNA）是一类新的RNA分子，越来越多地被认为是实体瘤和血液系统恶性肿瘤的重要分子参与者。在此，我们研究了长链非编码RNA表达是否与临床和分子特征相关，以及年轻成人（年龄<60岁）新发细胞遗传学正常的急性髓性白血病的预后。在训练组（n=263）和验证组（n=114）中进行全转录组分析。使用训练集，我们确定了24个与无事件生存相关的长非编码RNA。这些转录物的加权表达值的线性组合产生预后评分。在验证集中，高分患者的无病生存期（P<0.001）、总生存期（P=0.002）和无事件生存期（P<0.001）均短于低分患者。在多变量分析中，长链非编码RNA评分状态是无疾病（P=0.01）和无事件生存期（P=0.002）的独立预后标志物，并显示了总生存期的趋势（P=0.06）。在细胞遗传学正常的急性髓性白血病中具有预后意义的多种检测的分子改变中，仅双CEBPA突变、NPM 1突变和FLT 3-ITD与不同的长非编码RNA特征相关。长链非编码RNA评分与信使RNA和microRNA表达的相关性鉴定了具有高分的患者中参与淋巴细胞/白细胞活化、炎症和凋亡的基因的富集。我们的结论是，长的非编码RNA分析提供了有意义的预后信息，在年轻的成年人与细胞遗传学正常的急性髓细胞白血病。此外，预后性长非编码RNA的表达与该疾病中的致癌分子通路相关。clinicaltrials.gov标识符：00048958（CALGB-8461）、00899223（CALGB-9665）和00900224（CALGB-20202）。
Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202).
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影响因子：
37.3
作者：
Gibb EA;Brown CJ;Lam WL
通讯作者：
Lam WL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
--
作者：
Crea F;Watahiki A;Quagliata L;Xue H;Pikor L;Parolia A;Wang Y;Lin D;Lam WL;Farrar WL;Isogai T;Morant R;Castori-Eppenberger S;Chi KN;Wang Y;Helgason CD
通讯作者：
Helgason CD
影响因子：
64.8
作者：
BARTOLOMEI, MS;ZEMEL, S;TILGHMAN, SM
通讯作者：
TILGHMAN, SM