ArticleCancer cell2026
RAF-independent MEK mutations drive refractory histiocytic neoplasms but respond to ERK inhibition.
2 registry-linked trialsAbstract read
In one paragraph
Article in Cancer cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Registry for Patients With Erdheim-Chester Disease and Other Histiocytoses
A Multi-center, Open-label, Single-arm Study of Luvometinib Monotherapy in Pediatric Langerhans Cell Histiocytosis With Single-system Special-site Single and Multifocal Bone Involvement
Who cites it
5 citing papers in PubMed.
- Langerhans cell histiocytosis: molecular mechanisms underlying pathogenesis and emerging targeted therapeutics.Cancer metastasis reviews · 2026Review
- Class 3 MAP2K1 mutations associate with relapse and multiple treatment lines in multisystem Langerhans cell histiocytosis.Blood advances · 2026Article
- Histiocytosis development and clinical variation through the lens of genomics.The Journal of pathology · 2026Review
- Efficacy, safety, and relapse outcomes of MAPK inhibitors in pediatric Langerhans cell histiocytosis: A real-world study.International journal of cancer · 2026Article
- A systematic evaluation of protein allosteric site prediction tools with independent datasets.Journal of computer-aided molecular design · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
45 authors.
Eli L DiamondDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jean-Francois EmileParis-Saclay University, Versailles SQY University, EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Smart Imaging, Service de Pathologie, 92100 Boulogne, France.
Takeshi FujinoMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Julien HarocheSorbonne University, Assistance Publique-Hôpitaux de Paris, Pitié-Salpȇtrière Hospital, Internal Medicine Department 2, French Reference Centre for Histiocytosis, CIMI INSERM-UMRS 1135, 75013 Paris, France.
Maxim I MaronMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alexander M LewisMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jahan RahmanMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Anne S ReinerDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Dana BossertDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Marc RosenblumDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mariko YabeDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Kseniya Petrova-DrusDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jasmine H FrancisOphthalmic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Veronica RotembergDermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Raajit K RampalLeukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sarah YooLeukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Anthony F DaniyanLeukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sonia MahajanDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Vaios HatzoglouDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Robert YoungDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Gary A UlanerDepartment of Molecular Imaging and Therapy, Hoag Family Cancer Institute, Irvine, CA, USA; Radiology and Translational Genomics, University of Southern California, Los Angeles, CA 90033, USA.
Wiebke RöslerDepartment of Hematology and Oncology, University Hospital, 8091 Zurich, Switzerland.
Oshrat Hershkovitz-RokahDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel; Translational Research Lab, Assuta Medical Centers, Tel-Aviv 52456, Israel.
Ofer ShpilbergAdelson School of Medicine, Ariel University, Ariel 40700, Israel; Institute of Hematology, Assuta Medical Centers, Tel-Aviv 52456, Israel.
Roei D MazorInstitute of Hematology, Assuta Medical Centers, Tel-Aviv 52456, Israel.
Luke Y C ChenDivision of Hematology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Michael SingerMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
M Adriana CuibusMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Kenyon WeisMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Salima BenbarcheMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pu ZhangMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Nina FoxMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cynthia CastroMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Steven TittleyMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Matthew WitkowskiDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Fleur Cohen-AubartSorbonne University, Assistance Publique-Hôpitaux de Paris, Pitié-Salpȇtrière Hospital, Internal Medicine Department 2, French Reference Centre for Histiocytosis, CIMI INSERM-UMRS 1135, 75013 Paris, France.
Louis TerriouService de Médecine Interne et Immunologie Clinique, Hôpital Claude Huriez, 59037 Lille, France.
Maher HanounDepartment of Hematology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Nicolas SchleinitzDépartement de Médecine Interne, CHU Timone, AP-HM, Aix-Marseille Université, 13007 Marseille, France.
Gabriela SosaServicio de Endocrinología Sanatorio Allende, Córdoba X5000, Argentina.
Timo HautalaResearch Unit of Internal Medicine and Biomedicine, University of Oulu, 90570 Oulu, Finland.
Laure Farnault De LassusService d'Hématologie, Hopital de la Conception, AP-HM, 13385 Marseille, France.
Neal RosenMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Omar Abdel-WahabMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abdelwao@mskcc.org.
Benjamin H DurhamMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Departments of Pediatrics and Pathology and Laboratory Medicine, Rutgers Cancer Institute, New Brunswick, NJ 08901, USA. Electronic address: bd559@cinj.rutgers.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MThe Memorial Sloan Kettering Cancer Center SPORE in LeukemiaP50CA254838 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Eytan Stein · 2021 to 2026
$16.8MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MMolecular Pathogenesis and Therapy of Systemic Histiocytic NeoplasmsR37CA259260 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Eli Lous Diamond · 2021 to 2026
$3.3MInterrogating the minor spliceosome to understand and treat leukemiaR01CA251138 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, BRADLEY, ROBERT K · 2020 to 2024
$3.3MSynthetic introns for selective targeting of RNA splicing factor-mutant leukemiaR01CA283364 · NCI · FRED HUTCHINSON CANCER CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2023 to 2026
$2.9MTargeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7MOrigins of BRAF-mutant hematologic malignancies and their therapeutic resistanceR01CA201247 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, PARK, CHRISTOPHER Y · 2016 to 2020
$2.7MUnderstanding and Targeting Aberrant RNA Splicing in LeukemiaR35CA304457 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Omar Abdel-Wahab · 2025 to 2026
$2.0MCellular Origins, Molecular Pathogenesis, and Novel Therapeutic Strategies for MAP Kinase-Driven Hematological MalignanciesK08CA218901 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DURHAM, BENJAMIN HEATH · 2018 to 2022
$1.0MNCI NIH HHS K08 CA218901NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA254838NCI NIH HHS R01 CA201247NCI NIH HHS R01 CA242020NCI NIH HHS R01 CA251138NCI NIH HHS R01 CA283364NCI NIH HHS R35 CA304457NCI NIH HHS R37 CA259260NHLBI NIH HHS R01 HL128239
Abstract
Histiocytic neoplasms are clonal disorders of the monocyte/macrophage lineage defined by mutations activating mitogen-activated protein kinase (MAPK) signaling. Recently, the MEK1/2 inhibitor cobimetinib was FDA-approved for patients with adult histiocytoses. Here, aided by a prospective registry of patients with histiocytoses (NCT03329274), we identify that MEK1/2 mutations which constitutively activate MEK independently of RAF are associated with worse progression-free survival with MEK1/2 inhibition as compared to patients with other MEK1/2 mutational classes. The most common RAF-independent MEK1 mutation (MEK1
Indexed as
MAP Kinase Kinase 1MAP Kinase Kinase 2MutationProtein Kinase InhibitorsAdultAnimalsAzetidinesDrug Resistance, NeoplasmFemaleHumansMaleMAP Kinase Signaling SystemMiceMiddle AgedObservational Studies as TopicPiperidinesAzetidinescobimetinibMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2PiperidinesProtein Kinase InhibitorsBRAFcobimetinibErdheim-Chester diseaseERKhistiocytosesLangerhans cell histiocytosismacrophageMEKtrametinibulixertinib
Identifiers
What OpenQuestion holds
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Read underepoch 390
Registered trials
NCT03329274ClinicalTrials.gov
NCT07371182ClinicalTrials.gov
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.