Subtype-specific regulatory network rewiring in acute myeloid leukemia

被引：127

作者：

Assi, Salam A. ^{[1
]}

Imperato, Maria Rosaria ^{[1
]}

Coleman, Daniel J. L. ^{[1
]}

Pickin, Anna ^{[1
]}

Potluri, Sandeep ^{[1
]}

Ptasinska, Anetta ^{[1
]}

Chin, Paulynn Suyin ^{[1
]}

Blair, Helen ^{[2
]}

Cauchy, Pierre ^{[1
]}

James, Sally R. ^{[3
]}

Zacarias-Cabeza, Joaquin ^{[1
]}

Gilding, L. Niall ^{[1
]}

Beggs, Andrew ^{[1
]}

Clokie, Sam ^{[4
]}

Loke, Justin C. ^{[1
]}

Jenkin, Phil ^{[5
]}

Uddin, Ash ^{[5
]}

Delwel, Ruud ^{[6
,7
]}

Richards, Stephen J. ^{[8
]}

Raghavan, Manoj ^{[1
,9
]}

Griffiths, Michael J. ^{[4
]}

Heidenreich, Olaf ^{[2
,10
]}

Cockerill, Peter N. ^{[1
]}

Bonifer, Constanze ^{[1
]}

机构：

[1] Univ Birmingham, Inst Canc & Genom Sci, Birmingham, W Midlands, England

[2] Univ Newcastle, Northern Inst Canc Res, Newcastle, England

[3] Univ Leeds, Sect Expt Haematol, Leeds Inst Mol Med, Leeds, W Yorkshire, England

[4] Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Lab, Birmingham, W Midlands, England

[5] CMT Lab NHS Blood & Transplant, Birmingham, W Midlands, England

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

[7] Erasmus Univ, Oncode Inst, Erasmus MC, Med Ctr, Rotterdam, Netherlands

[8] St James Univ Hosp, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England

[9] Queen Elizabeth Hosp, Ctr Clin Haematol, Birmingham, W Midlands, England

[10] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

来源：

NATURE GENETICS | 2019年 / 51卷 / 01期

关键词：

HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTORS; EPIGENETIC REGULATORS; CHROMATIN-STRUCTURE; PROMOTER CONTACTS; T(8/21) AML; BINDING; DIFFERENTIATION; EXPRESSION; AML1-ETO;

D O I：

10.1038/s41588-018-0270-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of alterations in transcription factors, epigenetic regulators and signaling molecules. To determine how different mutant regulators establish AML subtype-specific transcriptional networks, we performed a comprehensive global analysis of cis-regulatory element activity and interaction, transcription factor occupancy and gene expression patterns in purified leukemic blast cells. Here, we focused on specific subgroups of subjects carrying mutations in genes encoding transcription factors (RUNX1, CEBP alpha), signaling molecules (FTL3-ITD, RAS) and the nuclear protein NPM1). Integrated analysis of these data demonstrates that each mutant regulator establishes a specific transcriptional and signaling network unrelated to that seen in normal cells, sustaining the expression of unique sets of genes required for AML growth and maintenance.

引用

页码：151 / +

页数：15

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