Evidence map›Paper›PMID 25027513›Full record

ArticleLeukemia2015

A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias.

A E Conway, J M Haldeman, D S Wechsler, C P Lavau

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

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

32 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Therapeutic targeting of exportin-1 beyond nuclear export.Trends in pharmacological sciences · 2025
    Review
  12. Article
  13. Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?International journal of molecular sciences · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

4 authors at 2 institutions in 1 country.

A E ConwayDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
J M HaldemanDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
D S Wechsler1] Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA [2] Division of Pediatric Hematology-Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
C P LavauDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Duke Medical Center · USDuke University · US

Funding

ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
Mechanisms of Leukemogenic Transformation by MLL-CALMR01CA109281 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WECHSLER, DANIEL STEVEN · 2005 to 2009
$1.3M
NCI NIH HHS R01 CA 109281NCI NIH HHS R01 CA109281NIGMS NIH HHS T32 GM007184
6 · The paper itself

Abstract

The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor.

Indexed as

Gene Expression Regulation, LeukemicAnimalsCell Line, TumorCell Transformation, NeoplasticChromatin ImmunoprecipitationExportin 1 ProteinFatty Acids, UnsaturatedFibroblastsGene Expression ProfilingHEK293 CellsHomeodomain ProteinsHumansKaryopherinsLuciferasesMiceMultigene FamilyAF10-CALM fusion protein, humanExportin 1 ProteinFatty Acids, UnsaturatedHomeodomain ProteinsHoxA proteinKaryopherinsleptomycin BLuciferasesOncogene Proteins, FusionReceptors, Cytoplasmic and Nuclear

Identifiers

PMID25027513
PMCPMC4297268
OpenAlexW2086598626

What OpenQuestion holds

Textmetadata
LicenceTDM
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.