Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets.
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.
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.
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Maiga
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.|Department of Computer Science and Operations Research, Université de Montréal, Montréal, Québec, Canada.
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Lemieux
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.
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Pabst
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.|Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.
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Lavallée
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.|Department of Biochemistry, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
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Bouvier
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.|Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.|Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.|Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
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Sauvageau
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.|Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.|Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.|Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
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Hébert
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
D018952:Antigens, CD34; D009363:Neoplasm Proteins; D043562:Receptors, G-Protein-Coupled