Evidence map›Paper›PMID 28816238›Full record

ArticleLeukemia2018

Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion.

B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto and 8 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03964922 (Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy), which is not on this map. Cited by 267 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
267citing papers in PubMed, 1 pooled it
16.6field-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.

NCT03964922 naunknown statusnot on this mapstarted 2019, after this paper: background citation

Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation

TypeinterventionalSponsorCentral Hospital, Nancy, FranceRan2019 to 2022Enrolled104ConditionsRelapse Leukemia, Allogeneic Stem Cell Transplantation, Immune Evasion, TumorArmsblood sample, bone marrow sample
3 · Its place in the literature

Who cites it

267 citing papers in PubMed, 1 synthesis or guideline pooled it, 429 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Niche-derived exosomes controlFrontiers in immunology · 2026
    Article
  19. Review
  20. Review

207 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

18 authors at 4 institutions in 2 countries.

B KumarDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
M GarciaDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
L WengDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
X JungDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
J L MurakamiDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
X HuDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.ORCID 0000-0002-3952-3373
T McDonaldDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
A LinDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
A R KumarDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
D L DiGiustoDepartment of Pediatric Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA.
A S SteinDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
V A PullarkatDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
S K HuiDepartment of Radiation Oncology, City of Hope, Duarte, CA, USA.
N CarlessoDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Y-H KuoDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
R BhatiaDivision of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
G MarcucciDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
C-C ChenDivison of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
City of Hope · USCincinnati Children's Hospital Medical Center · USStanford Medicine · USUniversity of Alabama at Birmingham · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
Targeting MicroRNAs to Eradicate Leukemia Stem CellsR01CA205247 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KUO, YA-HUEI, MARCUCCI, GUIDO · 2017 to 2025
$4.8M
Physiologic Regulation of Hematopoiesis by NotchR01DK097837 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI CARLESSO, NADIA · 2014 to 2017
$1.6M
Paired lg-Like Receptor as a Regulator of Hematopoietic Stem Cell FunctionR00HL087936 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, CHING-CHENG · 2010 to 2012
$747k
Role of a4b7 integrin/MAdCAM-1 interaction in hematopoietic stem cell traffickingF31HL114393 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI MURAKAMI, JODI LEHIWA KAZUYO · 2013 to 2016
$70k
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA205247NHLBI NIH HHS F31 HL114393NHLBI NIH HHS R00 HL087936NIDDK NIH HHS R01 DK097837
6 · The paper itself

Abstract

Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth. Conversely, disruption of exosome secretion in AML cells through targeting Rab27a, an important regulator involved in exosome release, significantly delayed leukemia development. In BM stromal cells, AML-derived exosomes induced the expression of DKK1, a suppressor of normal hematopoiesis and osteogenesis, thereby contributing to osteoblast loss. Conversely, treatment with a DKK1 inhibitor delayed AML progression and prolonged survival in AML-engrafted mice. In addition, AML-derived exosomes induced a broad downregulation of hematopoietic stem cell-supporting factors (for example, CXCL12, KITL and IGF1) in BM stromal cells and reduced their ability to support normal hematopoiesis. Altogether, this study uncovers novel features of AML pathogenesis and unveils how AML cells create a self-strengthening leukemic niche that promotes leukemic cell proliferation and survival, while suppressing normal hematopoiesis through exosome secretion.

Indexed as

Tumor MicroenvironmentAnimalsBiomarkersBone MarrowCell LineCoculture TechniquesDisease Models, AnimalExosomesHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansIntercellular Signaling Peptides and ProteinsLeukemia, Myeloid, AcuteMesenchymal Stem CellsMiceMice, KnockoutBiomarkersDkk1 protein, mouseIntercellular Signaling Peptides and Proteins

Identifiers

PMID28816238
PMCPMC5843902
OpenAlexW2747254185

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

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.