Evidence map›Paper›PMID 38218188›Full record

ArticleCell2024

Inherited blood cancer predisposition through altered transcription elongation.

Jiawei Zhao, Liam D Cato, Uma P Arora, Erik L Bao, Samuel C Bryant, Nicholas Williams, Yuemeng Jia, Seth R Goldman, Jyoti Nangalia, Michael A Erb and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
10.9field-weighted citation impact, top 1% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

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  15. Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

13 authors at 6 institutions in 3 countries.

Jiawei ZhaoDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Immunology, Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China. Electronic address: jw.zhao3@siat.ac.cn.
Liam D CatoDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Uma P AroraDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Erik L BaoDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samuel C BryantBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas WilliamsWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; UK and MRC-Wellcome Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Yuemeng JiaHarvard Stem Cell Institute, Cambridge, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Seth R GoldmanNascent Transcriptomics Core, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Jyoti NangaliaWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; UK and MRC-Wellcome Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Michael A ErbDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Seychelle M VosDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Scott A ArmstrongDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vijay G SankaranDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA. Electronic address: sankaran@broadinstitute.org.
Broad Institute · USWellcome/MRC Cambridge Stem Cell Institute · GBBoston Children's Hospital · USHarvard University · USHoward Hughes Medical Institute · USScripps Research Institute · US

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
PATHOPHYSIOLOGY OF HUMAN BLOOD CELLST32HL007574 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Daniel Evan Bauer · 1985 to 2026
$18.4M
Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7M
Selective pressures from inherited variation impacting myeloproliferative neoplasm initiationR01CA265726 · NCI · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2022 to 2026
$2.5M
Medical Research Council MC_PC_17230NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA265726NHLBI NIH HHS R01 HL146500NIDDK NIH HHS R01 DK103794
6 · The paper itself

Abstract

Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a ∼10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewal. By following up on insights from a human genetic study examining inherited predisposition to the myeloid malignancies, we define a previously unknown antagonistic interaction between the PAF1 and super elongation complexes. These insights could enable targeted approaches for blood cancer prevention.

Indexed as

Hematologic NeoplasmsPhosphoproteinsTranscription Elongation, GeneticTranscription FactorsHematopoietic Stem CellsHumansNuclear ProteinsCTR9 protein, humanNuclear ProteinsPAF1 protein, humanPhosphoproteinsTranscription Factorscancer predispositionCTR9hematopoiesishematopoietic stem cellsmyeloid malignanciesPAF1 complexself-renewalsuper elongation complextranscription elongation

Identifiers

PMID38218188
PMCPMC10872907
OpenAlexW4390825675

What OpenQuestion holds

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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.