Evidence map›Paper›PMID 25535865›Full record

ArticleStem cell research2015

Long term maintenance of myeloid leukemic stem cells cultured with unrelated human mesenchymal stromal cells.

Sawa Ito, A John Barrett, Amalia Dutra, Evgenia Pak, Samantha Miner, Keyvan Keyvanfar, Nancy F Hensel, Katayoun Rezvani, Pawel Muranski, Paul Liu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  8. Review
  9. Immune Biology of Acute Myeloid Leukemia: Implications for Immunotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Review
  10. Review
  11. Review
  12. Article
  13. Murine Models of Acute Myeloid Leukaemia.International journal of molecular sciences · 2019
    Review
  14. Article
  15. Article
  16. Role of the microenvironment in myeloid malignancies.Cellular and molecular life sciences : CMLS · 2018
    Review
  17. Review
  18. Review
  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

12 authors at 2 institutions in 1 country.

Sawa ItoHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
A John BarrettHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amalia DutraCytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Evgenia PakCytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Samantha MinerHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Keyvan KeyvanfarHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nancy F HenselHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Katayoun RezvaniUniversity of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pawel MuranskiHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Paul LiuOncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Andre Larochelle *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Joseph Melenhorst *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
National Institutes of Health · USThe University of Texas MD Anderson Cancer Center · US

Funding

NHGRI/DIR Cytogenetics and Microscopy CoreZICHG200348 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI WINCOVITCH, STEPHEN · 2010 to 2025
$20.3M
MOLECULAR PATHOGENESIS OF CHROMOSOME 16 INVERSION INHUMAN LEUKEMIAZIAHG000030 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI LIU, PAUL · 2009 to 2025
$15.8M
Regenerative Therapies for Inherited Blood Disorders-Gene therapyZIAHL006172 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LAROCHELLE, ANDRE · 2013 to 2025
$13.0M
Characterization and improvement of graft versus leukemia effectsZIAHL006107 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BARRETT, AUSTIN JOHN · 2011 to 2017
$8.6M
Immunobiology and immunotherapy of leukemiaZIAHL006106 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BARRETT, AUSTIN JOHN · 2011 to 2017
$8.6M
Regenerative Therapies for Inherited Blood Disorders-iPSC differentiationZIAHL006217 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LAROCHELLE, ANDRE · 2016 to 2025
$8.5M
GRAFT-VERSUS-LEUKEMIAZ01HL002342 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BARRETT, AUSTIN JOHN · 1994 to 2008
$7.7M
Investigation of the mechanisms of action of eltrombopagZIAHL006205 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LAROCHELLE, ANDRE · 2015 to 2025
$6.8M
Regenerative Therapies for Inherited Blood Disorders-HSC expansionZIAHL006218 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LAROCHELLE, ANDRE · 2016 to 2022
$3.2M
Intramural NIH HHS Z01 HL002342Intramural NIH HHS Z99 HL999999
6 · The paper itself

Abstract

Mesenchymal stromal cells (MSCs) support the growth and differentiation of normal hematopoietic stem cells (HSCs). Here we studied the ability of MSCs to support the growth and survival of leukemic stem cells (LSCs) in vitro. Primary leukemic blasts isolated from the peripheral blood of 8 patients with acute myeloid leukemia (AML) were co-cultured with equal numbers of irradiated MSCs derived from unrelated donor bone marrow, with or without cytokines for up to 6weeks. Four samples showed CD34(+)CD38(-) predominance, and four were predominantly CD34(+)CD38(+). CD34(+) CD38(-) predominant leukemia cells maintained the CD34(+) CD38(-) phenotype and were viable for 6weeks when co-cultured with MSCs compared to co-cultures with cytokines or medium only, which showed rapid differentiation and loss of the LSC phenotype. In contrast, CD34(+) CD38(+) predominant leukemic cells maintained the CD34(+)CD38(+) phenotype when co-cultured with MSCs alone, but no culture conditions supported survival beyond 4weeks. Cell cycle analysis showed that MSCs maintained a higher proportion of CD34(+) blasts in G0 than leukemic cells cultured with cytokines. AML blasts maintained in culture with MSCs for up to 6weeks engrafted NSG mice with the same efficiency as their non-cultured counterparts, and the original karyotype persisted after co-culture. Chemosensitivity and transwell assays suggest that MSCs provide pro-survival benefits to leukemic blasts through cell-cell contact. We conclude that MSCs support long-term maintenance of LSCs in vitro. This simple and inexpensive approach will facilitate basic investigation of LSCs and enable screening of novel therapeutic agents targeting LSCs.

Indexed as

ADP-ribosyl Cyclase 1AnimalsAntigens, CD34Antimetabolites, AntineoplasticApoptosisCells, CulturedCoculture TechniquesCytarabineHumansImmunophenotypingInterleukin-3KaryotypingLeukemia, Myeloid, AcuteMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiceADP-ribosyl Cyclase 1Antigens, CD34Antimetabolites, AntineoplasticCytarabineInterleukin-3Stem Cell Factor

Identifiers

PMID25535865
PMCPMC4634876
OpenAlexW1968611056

What OpenQuestion holds

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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.