Evidence map›Paper›PMID 36746437›Full record

ArticleBritish journal of haematology2023

Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors.

Chang-Bin Jing, Nicole Prutsch, Shuning He, Mark W Zimmerman, Yosef Landesman, A Thomas Look

Open access · hybridAbstract read
In one paragraph

Article in British journal of haematology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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  7. Depletion ofFrontiers in hematology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Chang-Bin JingDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Nicole PrutschDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Shuning HeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Mark W ZimmermanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Yosef LandesmanKaryopharm Therapeutics, Newton, Massachusetts, USA.
A Thomas LookDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-7851-8617
Harvard University · USBoston Children's Hospital · USKaryopharm Therapeutics (United States) · US

Funding

Mechanisms and Vulnerabilities of Aberrant Transcriptional Enhancers in CancerR35CA210064 · NCI · DANA-FARBER CANCER INST · PI LOOK, A. THOMAS · 2016 to 2022
$7.3M
NCI NIH HHS R35 CA210064
6 · The paper itself

Abstract

TET2 inactivating mutations serve as initiating genetic lesions in the transformation of haematopoietic stem and progenitor cells (HSPCs). In this study, we analysed known drugs in zebrafish embryos for their ability to selectively kill tet2-mutant HSPCs in vivo. We found that the exportin 1 (XPO1) inhibitors, selinexor and eltanexor, selectively kill tet2-mutant HSPCs. In serial replating colony assays, these small molecules were selectively active in killing murine Tet2-deficient Lineage-, Sca1+, Kit+ (LSK) cells, and also TET2-inactivated human acute myeloid leukaemia (AML) cells. Selective killing of TET2-mutant HSPCs and human AML cells by these inhibitors was due to increased levels of apoptosis, without evidence of DNA damage based on increased γH2AX expression. The finding that TET2 loss renders HSPCs and AML cells selectively susceptible to cell death induced by XPO1 inhibitors provides preclinical evidence of the selective activity of these drugs, justifying further clinical studies of these small molecules for the treatment of TET2-mutant haematopoietic malignancies, and to suppress clonal expansion in age-related TET2-mutant clonal haematopoiesis.

Indexed as

DioxygenasesLeukemia, Myeloid, AcuteAmidesAnimalsDNA-Binding ProteinsExportin 1 ProteinHematopoietic Stem CellsHumansMicePyrimidinesZebrafishAmidesDioxygenasesDNA-Binding ProteinsEltanexorExportin 1 ProteinPyrimidinesTET2 protein, humanTet2 protein, mouseclonal haematopoiesiseltanexorHSPCselinexorTET2XPO1

Identifiers

PMID36746437
PMCPMC10121884
OpenAlexW4319299499

What OpenQuestion holds

Textmetadata
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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.