A somatic mutation of GFI1B identified in leukemia alters cell fate via a SPI1 (PU.1) centered genetic regulatory network

被引：18

作者：

Anguita, Eduardo ^{[1
]}

Gupta, Rajeev ^{[2
]}

Olariu, Victor ^{[3
]}

Valk, Peter J. ^{[4
]}

Peterson, Carsten ^{[3
]}

Delwel, Ruud ^{[4
]}

Enver, Tariq ^{[2
]}

机构：

[1] Hosp Clin San Carlos IdISSC, Dept Hematol, Prof Martin Lagos S-N, Madrid 28040, Spain

[2] UCL Canc Inst, Paul OGorman Bldg 72 Huntley St, London WC1E 6BT, England

[3] Lund Univ, Computat Biol & Biol Phys Div, Lund, Sweden

[4] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands

来源：

DEVELOPMENTAL BIOLOGY | 2016年 / 411卷 / 02期

关键词：

GFI1B; SPI1; PU.1; Transcriptional networks; Acute myeloid leukemia; Myelodysplastic syndrome; TRANSCRIPTION FACTOR-BINDING; ZINC-FINGER PROTEIN; HEMATOPOIETIC STEM; GFI-1B; EXPRESSION; DIFFERENTIATION; NEUTROPENIA; REQUIREMENT; MACROPHAGE; REPRESSION;

D O I：

10.1016/j.ydbio.2016.02.002

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We identify a mutation (D262N) in the erythroid-affiliated transcriptional repressor GFI1B, in an acute myeloid leukemia (AML) patient with antecedent myelodysplastic syndrome (MDS). The GFI1B-D262N mutant functionally antagonizes the transcriptional activity of wild-type GFI1B. GFI1B-D262N promoted myelomonocytic versus erythroid output from primary human hematopoietic precursors and enhanced cell survival of both normal and MDS derived precursors. Re-analysis of AML transcriptome data identifies a distinct group of patients in whom expression of wild-type GFI1B and SPIT (PU.1) have an inverse pattern. In delineating this GFI1B-SPI1 relationship we show that (i) SPI1 is a direct target of GFI1B, (ii) expression of GFI1B-D262N produces elevated expression of SPI1, and (iii) SPIT-knockdown restores balanced lineage output from GFI1B-D262N-expressing precursors. These results table the SPI1-GFI1B transcriptional network as an important regulatory axis in AML as well as in the development of erythroid versus myelomonocytic cell fate. (C) 2016 Published by Elsevier Inc.

引用

页码：277 / 286

页数：10

共 52 条

[51] PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway [J].

Zhou, J. ;

Wu, J. ;

Li, B. ;

Liu, D. ;

Yu, J. ;

Yan, X. ;

Zheng, S. ;

Wang, J. ;

Zhang, L. ;

He, F. ;

Li, Q. ;

Chen, A. ;

Zhang, Y. ;

Zhao, X. ;

Guan, Y. ;

Zhao, X. ;

Yan, J. ;

Ni, J. ;

Nobrega, M. A. ;

Loewenberg, B. ;

Delwel, R. ;

Valk, P. J. M. ;

Kumar, A. ;

Xie, L. ;

Tenen, D. G. ;

Huang, G. ;

Wang, Q-f .

LEUKEMIA, 2014, 28 (07) :1436-1448

[52]

ZweidlerMcKay PA, 1996, MOL CELL BIOL, V16, P4024

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