Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature

被引：54

作者：

Cauchy, Pierre ^{[1
]}

James, Sally R. ^{[2
]}

Zacarias-Cabeza, Joaquin ^{[1
]}

Ptasinska, Anetta ^{[1
]}

Imperato, Maria Rosaria ^{[1
]}

Assi, Salam A. ^{[2
]}

Piper, Jason ^{[3
]}

Canestraro, Martina ^{[1
]}

Hoogenkamp, Maarten ^{[1
]}

Raghavan, Manoj ^{[1
,4
]}

Loke, Justin ^{[1
]}

Akiki, Susanna ^{[5
]}

Clokie, Samuel J. ^{[5
]}

Richards, Stephen J. ^{[6
]}

Westhead, David R. ^{[7
]}

Griffiths, Michael J. ^{[1
,5
]}

Ott, Sascha ^{[3
]}

Bonifer, Constanze ^{[1
]}

Cockerill, Peter N. ^{[8
]}

机构：

[1] Univ Birmingham, Coll Med & Dent, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England

[2] Univ Leeds, Leeds Inst Mol Med, Sect Expt Haematol, Leeds LS9 7TF, W Yorkshire, England

[3] Univ Warwick, Warwick Syst Biol Ctr, Coventry CV4 7AL, W Midlands, England

[4] Queen Elizabeth Hosp, Ctr Clin Haematol, Birmingham B15 2TH, W Midlands, England

[5] Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Lab, Birmingham B15 2TG, W Midlands, England

[6] St James Univ Hosp, Haematol Malignancy Diagnost Serv, Leeds LS9 7TF, W Yorkshire, England

[7] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England

[8] Univ Birmingham, Coll Med & Dent, Sch Immun & Infect, Birmingham B15 2TT, W Midlands, England

来源：

CELL REPORTS | 2015年 / 12卷 / 05期

基金：

英国工程与自然科学研究理事会;

关键词：

TRANSCRIPTION FACTORS; ACTIVE CHROMATIN; GENE-EXPRESSION; MUTATIONS; CELLS; DIFFERENTIATION; IDENTIFICATION; REGULATOR; SELECTION; NETWORK;

D O I：

10.1016/j.celrep.2015.06.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect the epigenetic regulatory machinery and signaling molecules, leading to a block in hematopoietic differentiation. Constitutive signaling from mutated growth factor receptors is a major driver of leukemic growth, but how aberrant signaling affects the epigenome in AML is less understood. Furthermore, AML cells undergo extensive clonal evolution, and the mutations in signaling genes are often secondary events. To elucidate how chronic growth factor signaling alters the transcriptional network in AML, we performed a system-wide multi-omics study of primary cells from patients suffering from AML with internal tandem duplications in the FLT3 transmembrane domain (FLT3-ITD). This strategy revealed cooperation between the MAP kinase (MAPK) inducible transcription factor AP-1 and RUNX1 as a major driver of a common, FLT3-ITD-specific gene expression and chromatin signature, demonstrating a major impact of MAPK signaling pathways in shaping the epigenome of FLT3-ITD AML.

引用

页码：821 / 836

页数：16

共 41 条

[1]

Emerging roles for chromatin as a signal integration and storage platform [J].