ArticleCancer cell2015
Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia.
Open access · bronzeAbstract read
In one paragraph
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
13.2field-weighted citation impact, top 1% of its field
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 121 citations in OpenAlex.
- Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.Blood · 2017Trial
- Genomic profiling of Mexican patients with B-cell precursor acute lymphoblastic leukemia reveals clinically significant somatic and potential germline variants.The journal of pathology. Clinical research · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Article
- Identification of Novel JAK2 Inhibitors from Amino Derivatives of Epoxyalantolactone: In Silico and In Vitro Studies.International journal of molecular sciences · 2025Article
- The Mechanisms of Resistance to JAK Inhibitors in Lymphoid Leukemias: A Scoping Review of Evidence from Preclinical Models and Case Reports.International journal of molecular sciences · 2025Article
- Plasmodiumfalciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity.Cell chemical biology · 2025Article
- JAK2 in pediatric leukemia: mechanisms of pathogenesis and drug development - a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- Article
- Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Review
- Exploring the therapeutic potential andFrontiers in pharmacology · 2025Article
- Selective metabolic regulations by p53 mutant variants in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- The roles of patient-derived xenograft models and artificial intelligence toward precision medicine.MedComm · 2024Review
- JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma.Science (New York, N.Y.) · 2024Article
- Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.Cancer discovery · 2024Article
- Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Type II mode of JAK2 inhibition and destabilization are potential therapeutic approaches against the ruxolitinib resistance driven myeloproliferative neoplasms.Frontiers in oncology · 2024Article
- Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches.Blood cancer discovery · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
41 authors at 5 institutions in 2 countries.
Shuo-Chieh WuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Loretta S LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Nadja KoppDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Joan MonteroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Bjoern ChapuyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Akinori YodaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Amanda L ChristieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Huiyun LiuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Alexandra ChristodoulouDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Diederik van BodegomDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jordy van der ZwetDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jacob V LayerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Trevor TiveyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Andrew A LaneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jeremy A RyanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Samuel Y NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Daniel J DeAngeloDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Richard M StoneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
David SteensmaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Martha WadleighDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Marian HarrisDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Emeline MandonNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Nicolas EbelNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Rita AndraosNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Vincent RomanetNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Arno DölemeyerNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Dario SterkerNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Michael ZenderNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Scott J RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Masato MurakamiNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Francesco HofmannNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Frank KuoDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Michael J EckDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Lewis B SilvermanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Stephen E SallanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Anthony LetaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Fabienne BaffertNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Eric VangrevelingheNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Thomas RadimerskiNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
Christoph GaulNovartis Institutes for Biomedical Research, 4002 Basel, Switzerland. Electronic address: christoph.gaul@novartis.com.
David M WeinstockDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address: dweinstock@partners.org.
Dana-Farber Cancer Institute · USNovartis (Switzerland) · CHNovartis Institutes for BioMedical ResearchBrigham and Women's Hospital · USBroad Institute · US
Funding
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1MResearch Training in Pediatric OncologyT32CA136432 · NCI · DANA-FARBER CANCER INST · PI SCOTT A ARMSTRONG · 2009 to 2026
$7.9MTraining Program in Molecular HematologyT32HL116324 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NANCY BERLINER · 2013 to 2026
$7.4MCRLF2 signaling in B-cell acute lymphoblastic leukemiaR01CA151898 · NCI · DANA-FARBER CANCER INST · PI WEINSTOCK, DAVID MARC · 2010 to 2019
$3.4MPolysomy 21 in Acute Lymphoblastic LeukemiaR01CA172387 · NCI · DANA-FARBER CANCER INST · PI WEINSTOCK, DAVID MARC · 2013 to 2017
$1.8MStructure and regulation of non-receptor tyrosine kinasesR01GM110352 · NIGMS · DANA-FARBER CANCER INST · PI ECK, MICHAEL J · 2014 to 2017
$1.7MTargeting Chromatin Modifications in Leukemia with Trisomy 21K08CA181340 · NCI · DANA-FARBER CANCER INST · PI LANE, ANDREW A · 2014 to 2018
$752kNCI NIH HHS K08 CA181340NCI NIH HHS R01 CA151898NCI NIH HHS R01CA151898-01NCI NIH HHS R01 CA172387NCI NIH HHS T32 CA009172NCI NIH HHS T32 CA136432NHLBI NIH HHS T32 HL116324NIGMS NIH HHS R01 GM110352
Abstract
A variety of cancers depend on JAK2 signaling, including the high-risk subset of B cell acute lymphoblastic leukemias (B-ALLs) with CRLF2 rearrangements. Type I JAK2 inhibitors induce paradoxical JAK2 hyperphosphorylation in these leukemias and have limited activity. To improve the efficacy of JAK2 inhibition in B-ALL, we developed the type II inhibitor CHZ868, which stabilizes JAK2 in an inactive conformation. CHZ868 potently suppressed the growth of CRLF2-rearranged human B-ALL cells, abrogated JAK2 signaling, and improved survival in mice with human or murine B-ALL. CHZ868 and dexamethasone synergistically induced apoptosis in JAK2-dependent B-ALLs and further improved in vivo survival compared to CHZ868 alone. These data support the testing of type II JAK2 inhibition in patients with JAK2-dependent leukemias and other disorders.
Indexed as
AminopyridinesAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCell Line, TumorCytoprotectionDexamethasoneDrug Resistance, NeoplasmDrug SynergismHumansJanus Kinase 2MiceMutationPrecursor Cell Lymphoblastic Leukemia-LymphomaAminopyridinesAntineoplastic AgentsBenzimidazolesCHZ868DexamethasoneJAK2 protein, humanJanus Kinase 2Protein Kinase Inhibitors
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.