ArticleCancer cell2018
Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS.
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78citing papers in PubMed
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78 citing papers in PubMed, 142 citations in OpenAlex.
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- Liquid-liquid phase separation and the formation of amyloid fibrils from DcpS scavenger enzymes.Scientific reports · 2026Article
- Integrated FHIT and IDH2 biomarker profiling predicts lethal sensitivity to DCPS inhibition in Acute Myeloid Leukemia and Myelodysplastic syndrome.Discover oncology · 2026Article
- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- Decapping scavenger enzyme as a promising biomarker in diabetic foot ulcers: A need for cautious interpretation.World journal of diabetes · 2026Article
- In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis.Nature communications · 2026Article
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- An SpC editor targeting pre-mRNA splicing for precise CRISPR control and enhanced antitumor efficacy.Nucleic acids research · 2025Article
- N7-methylguanosine-related gene decapping scavenger enzymes as a novel biomarker regulating epithelial cell function in diabetic foot ulcers.World journal of diabetes · 2025Article
- Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025Review
- DCPS is a synthetic lethal therapeutic target in acute myeloid leukemia expressing low levels of FHIT.Leukemia · 2025Article
- RNA kinetics influence the response to transcriptional perturbation in leukaemia cell lines.NAR cancer · 2024Article
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- A multiomics approach reveals RNA dynamics promote cellular sensitivity to DNA hypomethylation.Scientific reports · 2024Article
- Article
- Effect of the mRNA decapping enzyme scavenger (DCPS) inhibitor RG3039 on glioblastoma.Journal of translational medicine · 2024Article
- The RNA helicases DDX19A/B modulate selinexor sensitivity by regulating MCL1 mRNA nuclear export in leukemia cells.Leukemia · 2024Article
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
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- Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 9 institutions in 4 countries.
Takuji YamauchiDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan; Department of Stem Cell Biology and Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Takeshi MasudaDepartment of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Matthew C CanverDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Michael SeilerH3 Biomedicine, Inc., Cambridge, MA 02139, USA.
Yuichiro SembaDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Mohammad ShboulInstitute of Medical Biology, A∗STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
Mohammed Al-RaqadInstitute of Medical Biology, A∗STAR, 8A Biomedical Grove, Singapore 138648, Singapore; Al-Balqa Applied University, Faculty of Science, Al-Salt, Salt 19117, Jordan.
Manami MaedaDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Vivien A C SchoonenbergDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Mitchel A ColeDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Claudio Macias-TrevinoDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Yuichi IshikawaDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Qiuming YaoDepartment of Pathology & Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Michitaka NakanoDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Fumio AraiDepartment of Stem Cell Biology and Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Stuart H OrkinDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Bruno ReversadeInstitute of Medical Biology, A∗STAR, 8A Biomedical Grove, Singapore 138648, Singapore.
Silvia BuonamiciH3 Biomedicine, Inc., Cambridge, MA 02139, USA.
Luca PinelloDepartment of Pathology & Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Koichi AkashiDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan; Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Daniel E BauerDivision of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Takahiro MaedaDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan. Electronic address: t_maeda@cancer.med.kyushu-u.ac.jp.
Harvard University · USKyushu University · JPBoston Children's Hospital · USBrigham and Women's Hospital · USHarvard Stem Cell Institute · USInstitute of Medical Biology · SGAl-Balqa Applied University · JOCenter for Cancer Research · USKumamoto University · JP
Funding
TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI YIEN, YVETTE Y · 1985 to 2021
$38.9MCORE--ZEBRAFISHP30DK049216 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI ZHOU, YI · 1999 to 2015
$14.3MHigh-throughput discovery of essential noncoding sequences for erythropoiesisDP2HL137300 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN · 2016 to 2016
$2.7MTargeting the NuRD complex for fetal globin inductionR01DK111455 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BERLINER, NANCY, MAEDA, TAKAHIRO · 2016 to 2020
$2.0MDiscovering disease-causal variants by linking genetic and epigenetic variationR00HG008399 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI PINELLO, LUCA · 2017 to 2019
$747kEpigenetic regulation of BCL11A in the hemoglobin switchK08DK093705 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN · 2012 to 2016
$679kIdentification of sequences and factors required for HbF repressionR03DK109232 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN · 2016 to 2017
$226kTargeting the transcription machinery for fetal globin inductionR56DK105001 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI MAEDA, TAKAHIRO · 2015 to 2015
$142kIdentification of Novel Regulators of Fetal Hemoglobin ExpressionF30DK103359 · NIDDK · HARVARD MEDICAL SCHOOL · PI CANVER, MATTHEW CHARLES · 2015 to 2017
$131kNHGRI NIH HHS R00 HG008399NHLBI NIH HHS DP2 HL137300NHLBI NIH HHS P01 HL032262NIDDK NIH HHS F30 DK103359NIDDK NIH HHS K08 DK093705NIDDK NIH HHS P30 DK049216NIDDK NIH HHS R01 DK111455NIDDK NIH HHS R03 DK109232
Abstract
To identify novel targets for acute myeloid leukemia (AML) therapy, we performed genome-wide CRISPR-Cas9 screening using AML cell lines, followed by a second screen in vivo. Here, we show that the mRNA decapping enzyme scavenger (DCPS) gene is essential for AML cell survival. The DCPS enzyme interacted with components of pre-mRNA metabolic pathways, including spliceosomes, as revealed by mass spectrometry. RG3039, a DCPS inhibitor originally developed to treat spinal muscular atrophy, exhibited anti-leukemic activity via inducing pre-mRNA mis-splicing. Humans harboring germline biallelic DCPS loss-of-function mutations do not exhibit aberrant hematologic phenotypes, indicating that DCPS is dispensable for human hematopoiesis. Our findings shed light on a pre-mRNA metabolic pathway and identify DCPS as a target for AML therapy.
Indexed as
AnimalsCell LineCRISPR-Cas SystemsEndoribonucleasesHumansLeukemiaMaleMetabolic Networks and PathwaysMice, Inbred C57BLMuscular Atrophy, SpinalQuinazolinesRNA, MessengerRNA PrecursorsRNA Splicing5-((1-(2,6-dichlorobenzyl)piperidin-4-yl)methoxy)quinazoline-2,4-diamineDcpS protein, humanEndoribonucleasesQuinazolinesRNA, MessengerRNA Precursorsacute myeloid leukemiaCRISPR-Cas9 saturation mutagenesisdecapping enzymedrug repurposinggenome-wide CRISPR-Cas9 screeningmRNA decaypre-mRNA metabolismpre-mRNA splicing
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