ArticleScience translational medicine2026
Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.
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Article in Science translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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44 authors.
Camille VaganayInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0009-0000-6960-3297
Frank LingInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Lois M KellyInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0009-0008-2950-3089
Juliette CharlesInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0009-0004-6278-2105
Paul-Arthur MeslinInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0009-0005-6455-0831
Hélène PasquerInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-1626-0627
Rathana KimInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0002-9987-7237
Marie PassetInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-4620-8782
Matthieu DuchmannInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0002-7299-4572
Léa Pelissier-MenjaudInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Séverine LecourtInserm U1279, Gustave Roussy Institute, Paris-Saclay University, 94800 Villejuif, France.ORCID 0000-0002-3231-6398
Angela H SuDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.
Emmanuelle LatourInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Christopher F BassilDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-2692-8611
Gabriela AlexeDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.ORCID 0000-0002-5668-6297
Gael FortinInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-0461-1573
Duong Ho NhatInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Cécile CuleuxInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Carine LegrandInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0002-0992-3886
Sofiane FodilHematology Department, Saint Louis Hospital, AP-HP, 75010 Paris, France.ORCID 0000-0002-6713-1609
Tony HuynhHematology Department, Saint Louis Hospital, AP-HP, 75010 Paris, France.ORCID 0000-0002-0612-1124
Khansa SaadallahInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Azucena RamosKoch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Bérangère LombardCurie Institute, PSL Research University, Mass Spectrometry and Proteomics Facility, 75005 Paris, France.ORCID 0000-0001-9044-3662
Damarys LoewCurie Institute, PSL Research University, Mass Spectrometry and Proteomics Facility, 75005 Paris, France.ORCID 0000-0002-9111-8842
Christopher D DelaneyDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-4549-6869
Catherine LonchampInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Morgane FontaineInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Kim PacchiardiInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Anja KocijancicInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0009-0008-5460-6944
Lisa AziezCNRS UMR8104, Inserm U1016, Institut Cochin, University of Paris-Cité, 75014 Paris, France.ORCID 0009-0004-1840-6698
Nina FenouilleInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.
Marie SebertInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-4376-4097
Lionel AdèsInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0002-9020-8766
Emmanuel RaffouxInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-3925-7391
Michael T HemannKoch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-6776-2163
Emmanuelle ClappierInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0001-7098-092X
Lina BenajibaInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0001-5440-1115
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.ORCID 0000-0003-0218-7895
Kris C WoodDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-5887-2253
Raphaël ItzyksonInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-2139-6262
Antoine ForgetQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-0223-0312
Camille LobryInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0003-0550-4921
Alexandre PuissantInserm U1342, IRSL, Paris Saint-Louis Leukemia Institute, Saint Louis Hospital, University of Paris-Cité, 75010 Paris, France.ORCID 0000-0002-3997-9282
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2MLineage-specific signaling and targeting of PI3K gamma in myeloid malignanciesR01CA266389 · NCI · DUKE UNIVERSITY · PI Kris C. Wood · 2022 to 2026
$2.0MNCI NIH HHS R01 CA266389NIGMS NIH HHS T32 GM007171
Abstract
Chemotherapy resistance in acute myeloid leukemia (AML) remains a major clinical challenge. Integration of multiomic profiling and in vivo functional genomics revealed splicing dysregulation as a determinant of chemoresistance in AML. We uncovered a network involving the splicing regulator SRRM1 and the CLK1/4 and PAK1 kinase families as vulnerabilities in chemoresistant AML cells. Both kinase families are hyperactivated in chemoresistant cells, promoting SRRM1 phosphorylation and altering its scaffolding function. We also identified a relapse-associated
Indexed as
Drug Resistance, NeoplasmLeukemia, Myeloid, Acutep21-Activated KinasesProtein Serine-Threonine KinasesRNA-Binding ProteinsRNA SplicingAnimalsCell Line, TumorHumansMicep21-Activated KinasesProtein Serine-Threonine KinasesRNA-Binding Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.