Evidence map›Paper›PMID 34903620›Full record

ArticleCancer discovery2022

Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation.

Bappaditya Chandra, Nicole L Michmerhuizen, Hazheen K Shirnekhi, Swarnendu Tripathi, Brittany J Pioso, David W Baggett, Diana M Mitrea, Ilaria Iacobucci, Michael R White, Jingjing Chen and 19 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
15.2field-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

134 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Phase separation and the tumor microenvironment.Cell communication and signaling : CCS · 2026
    Review
  19. Review
  20. Article

74 more citing papers are in PubMed but not listed here.

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

29 authors at 3 institutions in 2 countries.

Bappaditya Chandra *Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Nicole L Michmerhuizen *Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9960-5119
Hazheen K Shirnekhi *Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Swarnendu Tripathi *Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Brittany J PiosoDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-0123-8905
David W BaggettDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Diana M MitreaDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Ilaria IacobucciDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2008-1365
Michael R WhiteDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Jingjing ChenIntegrated Biomedical Sciences Program, the University of Tennessee Health Science Center, Memphis, Tennessee.ORCID 0000-0003-4179-0371
Cheon-Gil ParkDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Huiyun WuDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Stanley PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Anna MedyukhinaCenter for Bioimage Informatics, St. Jude Children's Research Hospital Memphis, Tennessee.ORCID 0000-0001-5268-713X
Khaled KhairyCenter for Bioimage Informatics, St. Jude Children's Research Hospital Memphis, Tennessee.ORCID 0000-0002-9274-5928
Qingsong GaoDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Chunxu QuDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Sherif AbdelhamedDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-3319-2403
Scott D GormanDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Simranjot BawaDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Carolyn MaslankaDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Swati KingerDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-2053-0944
Priyanka DograDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Mylene C FerrolinoDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9693-8401
Danika Di GiacomoDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Cristina MecucciDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy.
Jeffery M KlcoDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2961-6960
Charles G MullighanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-1871-1850
Richard W KriwackiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9798-6018
St. Jude Children's Research Hospital · USRhodes College · USUniversity of Perugia · IT

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Translating genomic discoveries to improved outcomes for high risk acute leukemiaR35CA197695 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2017 to 2026
$11.4M
Project 4U54CA243124 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MULLIGHAN, CHARLES G. · 2019 to 2023
$10.5M
Role of Phase separation by fusion oncoproteins in oncogenesisR01CA246125 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DENIZ, ASHOK A, KRIWACKI, RICHARD W · 2020 to 2024
$3.2M
Childhood Hematological Malignancies Training ProgramT32CA236748 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2019 to 2026
$2.0M
Genetically faithful modeling of NUP98 rearrangement and co-alterations in acute myeloid leukemiaF32CA261011 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MICHMERHUIZEN, NICOLE · 2021 to 2023
$160k
Probing the prevalence and molecular mechanisms of phase separation by fusion oncoproteinsF32GM143847 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GORMAN, SCOTT DANIEL · 2021 to 2021
$48k
NCI NIH HHS F32 CA261011NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA246125NCI NIH HHS R35 CA197695NCI NIH HHS T32 CA236748NCI NIH HHS U54 CA243124NIGMS NIH HHS F32 GM143847
6 · The paper itself

Abstract

NUP98 fusion oncoproteins (FO) are drivers in pediatric leukemias and many transform hematopoietic cells. Most NUP98 FOs harbor an intrinsically disordered region from NUP98 that is prone to liquid-liquid phase separation (LLPS) in vitro. A predominant class of NUP98 FOs, including NUP98-HOXA9 (NHA9), retains a DNA-binding homeodomain, whereas others harbor other types of DNA- or chromatin-binding domains. NUP98 FOs have long been known to form puncta, but long-standing questions are how nuclear puncta form and how they drive leukemogenesis. Here we studied NHA9 condensates and show that homotypic interactions and different types of heterotypic interactions are required to form nuclear puncta, which are associated with aberrant transcriptional activity and transformation of hematopoietic stem and progenitor cells. We also show that three additional leukemia-associated NUP98 FOs (NUP98-PRRX1, NUP98-KDM5A, and NUP98-LNP1) form nuclear puncta and transform hematopoietic cells. These findings indicate that LLPS is critical for leukemogenesis by NUP98 FOs. SIGNIFICANCE: We show that homotypic and heterotypic mechanisms of LLPS control NUP98-HOXA9 puncta formation, modulating transcriptional activity and transforming hematopoietic cells. Importantly, these mechanisms are generalizable to other NUP98 FOs that share similar domain structures. These findings address long-standing questions on how nuclear puncta form and their link to leukemogenesis. This article is highlighted in the In This Issue feature, p. 873.

Indexed as

LeukemiaNuclear Pore Complex ProteinsCarcinogenesisCell NucleusChildHomeodomain ProteinsHumansOncogene Proteins, FusionRetinoblastoma-Binding Protein 2Homeodomain ProteinsKDM5A protein, humannuclear pore complex protein 98Nuclear Pore Complex ProteinsNup98 protein, humanOncogene Proteins, FusionPRRX1 protein, humanRetinoblastoma-Binding Protein 2

Identifiers

PMID34903620
PMCPMC8983581
OpenAlexW4200158487

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.