Evidence map›Paper›PMID 34131282›Full record

ArticleLeukemia2021

A novel leukemic route of mutant NPM1 through nuclear import of the overexpressed long noncoding RNA LONA.

Morgane Gourvest, Etienne De Clara, Hsin-Chieh Wu, Christian Touriol, Fabienne Meggetto, Hugues De Thé, Stéphane Pyronnet, Pierre Brousset, Marina Bousquet

Open access · bronzeAbstract read
In one paragraph

Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 35% 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

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Non-coding RNA · 2025
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (International journal of molecular sciences · 2023
    Review
  10. Article
  11. Mutant NPM1-Regulated FTO-Mediated mFrontiers in oncology · 2022
    Article
  12. Article
  13. Article
  14. Review
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

9 authors at 2 institutions in 1 country.

Morgane GourvestCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.ORCID http://orcid.org/0000-0003-4095-6691
Etienne De ClaraCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.
Hsin-Chieh WuINSERM U944 and 1050, IRSL, University of Paris and PSL, Hôpital St. Louis and Collège de France, Paris, France.
Christian TouriolCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.
Fabienne MeggettoCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.
Hugues De ThéINSERM U944 and 1050, IRSL, University of Paris and PSL, Hôpital St. Louis and Collège de France, Paris, France.ORCID http://orcid.org/0000-0002-1113-4472
Stéphane PyronnetCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.
Pierre BroussetCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France.
Marina BousquetCancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'excellence Toulouse Cancer (TOUCAN), Toulouse, France. bousquetmarina@gmail.com.ORCID http://orcid.org/0000-0001-8333-1144
Centre National de la Recherche Scientifique · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The most frequent genetic alteration in acute myeloid leukemia (AML) is the mutation of nucleophosmin 1 (NPM1). Yet, its downstream oncogenic routes are not fully understood. Here, we report the identification of one long noncoding RNA (lncRNA) overexpressed in NPM1-mutated AML patients (named LONA) whose intracellular localization inversely reflects that of NPM1. While NPM1 is nuclear and LONA cytoplasmic in wild-type NPM1 AML cells, LONA becomes nuclear as mutant NPM1 moves toward the cytoplasm. Gain or loss of function combined with a genome-wide RNA-seq search identified a set of LONA mRNA targets encoding proteins involved in myeloid cell differentiation (including THSB1, MAFB, and ASB2) and interaction with its microenvironment. Consistently, LONA overexpression in mutant NPM1 established cell lines and primary AML cells exerts an anti-myeloid differentiation effect, whilst it exerts an opposite pro-myeloid differentiation effect in a wild type NPM1 setting. In vivo, LONA overexpression acts as an oncogenic lncRNA reducing the survival of mice transplanted with AML cells and rendering AML tumors more resistant to AraC chemotherapy.These data indicate that mutation-dependent nuclear export of NPM1 leads to nuclear retention and consequent oncogenic functions of the overexpressed lncRNA LONA, thus uncovering a novel NPM1 mutation-dependent pathway in AML pathogenesis.

Indexed as

Active Transport, Cell NucleusAnimalsCarcinogenesisCell DifferentiationCell Line, TumorCell NucleusCytoplasmGene Expression Regulation, LeukemicHL-60 CellsHumansLeukemia, Myeloid, AcuteMaleMiceMice, Inbred NODMice, SCIDMutationNPM1 protein, humanNpm1 protein, mouseNuclear ProteinsNucleophosminRNA, Long NoncodingRNA, Messenger

Identifiers

PMID34131282
PMCPMC8205207
OpenAlexW3170082512

What OpenQuestion holds

Textmetadata
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.