2017年8月
Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia
NATURE GENETICS
- 巻
- 49
- 号
- 8
- 開始ページ
- 1274
- 終了ページ
- +
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ng.3900
- 出版者・発行元
- NATURE PUBLISHING GROUP
The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor(1), and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric TALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4(-)CD8(-)) or CD8(+) single-positive (SP) phenotype and had uniformly poor overall survival. These cases represent a subset of pediatric T-ALL distinguishable from the known T-ALL subsets(2) in terms of expression of genes involved in T cell precommitment, establishment of T cell identity, and post-beta-selection maturation and with respect to mutational profile. PU.1 fusion proteins retained transcriptional activity and, when constitutively expressed in mouse stem/progenitor cells, induced cell proliferation and resulted in a maturation block. Our findings highlight a unique role of SPI1 fusions in high-risk pediatric T-ALL.
- リンク情報
- ID情報
-
- DOI : 10.1038/ng.3900
- ISSN : 1061-4036
- eISSN : 1546-1718
- PubMed ID : 28671687
- Web of Science ID : WOS:000406397900019