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

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.