Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets

被引：61

作者：

Maiga, A. ^{[1
]}

Lemieux, S. ^{[1
,2
]}

Pabst, C. ^{[1
]}

Lavallee, V-P ^{[1
,3
]}

Bouvier, M. ^{[1
,4
]}

Sauvageau, G. ^{[1
,3
,5
,6
]}

Hebert, J. ^{[1
,3
,5
,6
]}

机构：

[1] Univ Montreal, IRIC, Montreal, PQ, Canada

[2] Univ Montreal, Dept Comp Sci & Operat Res, Montreal, PQ, Canada

[3] Hop Maison Neuve Rosemont, Div Hematol Oncol, 5415 Assompt Blvd, Montreal, PQ H1T 2M4, Canada

[4] Univ Montreal, Fac Med, Dept Biochem, Montreal, PQ H3C 3J7, Canada

[5] Hop Maison Neuve Rosemont, Leukemia Cell Bank Quebec, Montreal, PQ H1T 2M4, Canada

[6] Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3C 3J7, Canada

来源：

BLOOD CANCER JOURNAL | 2016年 / 6卷

基金：

加拿大创新基金会;

关键词：

CANCER CELLS; STEM-CELLS; CXCR4; ANTAGONIST; INHIBITION; EXPRESSION; MIGRATION; OVEREXPRESSION; PROLIFERATION; ACTIVATION;

D O I：

10.1038/bcj.2016.36

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups.

引用

页码：e431 / e431

页数：9

共 57 条

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