Evidence map›Paper›PMID 35152270›Full record

ArticleLeukemia2022

IPO11 regulates the nuclear import of BZW1/2 and is necessary for AML cells and stem cells.

Boaz Nachmias, Dilshad H Khan, Veronique Voisin, Arvind S Mer, Geethu Emily Thomas, Nadav Segev, Jonathan St-Germain, Rose Hurren, Marcela Gronda, Aaron Botham and 14 more

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

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  5. 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

24 authors at 4 institutions in 2 countries.

Boaz NachmiasPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-7341-2167
Dilshad H KhanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Veronique VoisinTerrence Donnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, Canada.
Arvind S MerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Geethu Emily ThomasPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Nadav SegevDepartment of Hematology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Jonathan St-GermainPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Rose HurrenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Marcela GrondaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Aaron BothamPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Xiaoming WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Neil MacleanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Ayesh K SeneviratnePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Nathan DuongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-7171-5554
Changjiang XuTerrence Donnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, Canada.
Andrea ArrudaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Elias OroujiPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-7413-1383
Arash AlgounehPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Razqallah HakemPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Liran ShlushDepartment of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Brian RaughtPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Gary D BaderTerrence Donnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, Canada.
Aaron D SchimmerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. aaron.schimmer@uhn.ca.ORCID http://orcid.org/0000-0003-4023-3899
University Health Network · CAUniversity of Toronto · CAHebrew University of Jerusalem · ILWeizmann Institute of Science · IL

Funding

CIHR
6 · The paper itself

Abstract

AML cells are arranged in a hierarchy with stem/progenitor cells giving rise to more differentiated bulk cells. Despite the importance of stem/progenitors in the pathogenesis of AML, the determinants of the AML stem/progenitor state are not fully understood. Through a comparison of genes that are significant for growth and viability of AML cells by way of a CRISPR screen, with genes that are differentially expressed in leukemia stem cells (LSC), we identified importin 11 (IPO11) as a novel target in AML. Importin 11 (IPO11) is a member of the importin β family of proteins that mediate transport of proteins across the nuclear membrane. In AML, knockdown of IPO11 decreased growth, reduced engraftment potential of LSC, and induced differentiation. Mechanistically, we identified the transcription factors BZW1 and BZW2 as novel cargo of IPO11. We further show that BZW1/2 mediate a transcriptional signature that promotes stemness and survival of LSC. Thus, we demonstrate for the first time how specific cytoplasmic-nuclear regulation supports stem-like transcriptional signature in relapsed AML.

Indexed as

beta KaryopherinsLeukemia, Myeloid, AcuteActive Transport, Cell NucleusCell Cycle ProteinsDNA-Binding ProteinsHumansNeoplastic Stem CellsStem Cellsbeta KaryopherinsBZW1 protein, humanBZW2 protein, humanCell Cycle ProteinsDNA-Binding ProteinsIPO11 protein, human

Identifiers

PMID35152270
PMCPMC9061300
OpenAlexW4220719076

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.