Evidence map›Paper›PMID 31613796›Full record

ArticleThe Journal of clinical investigation2020

Chronic myeloid leukemia stem cells require cell-autonomous pleiotrophin signaling.

Heather A Himburg, Martina Roos, Tiancheng Fang, Yurun Zhang, Christina M Termini, Lauren Schlussel, Mindy Kim, Amara Pang, Jenny Kan, Liman Zhao and 6 more

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

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

16 authors at 2 institutions in 1 country.

Heather A HimburgDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Martina RoosDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Tiancheng FangDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Yurun ZhangMolecular Biology Institute, UCLA, Los Angeles, California, USA.
Christina M TerminiDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Lauren SchlusselDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Mindy KimDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Amara PangDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Jenny KanDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Liman ZhaoDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Hyung SuhDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Joshua P SasineDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
Gopal SapparapuUCLA Clinical and Translational Science Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Peter M BowersUCLA Clinical and Translational Science Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Gary SchillerDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
John P ChuteDivision of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
University of California, Los Angeles · USSouthern California Clinical and Translational Science Institute · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Center for Biological RadioprotectorsU19AI067769 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCBRIDE, WILLIAM H. · 2005 to 2019
$44.6M
Semaphorin signaling regulates vascular and hematopoietic regenerationR01HL086998 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P · 2008 to 2022
$4.6M
Dkk1-Endothelial Progenitor Cell Treatment for the Mitigation of Hematopoietic Radiation InjuryU01AI138331 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HIMBURG, HEATHER A · 2018 to 2022
$3.0M
Epidermal growth factor mitigates radiation-induced hematopoietic failureU01AI107333 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P · 2013 to 2017
$2.6M
NCI NIH HHS P30 CA016042NHLBI NIH HHS R01 HL086998NIAID NIH HHS U01 AI107333NIAID NIH HHS U01 AI138331NIAID NIH HHS U19 AI067769
6 · The paper itself

Abstract

Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but the persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate the expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling, and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN has therapeutic potential to eradicate CML stem cells.

Indexed as

Signal TransductionAnimalsCarrier ProteinsCell SurvivalCytokinesFusion Proteins, bcr-ablHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMice, TransgenicNeoplastic Stem CellsCarrier ProteinsCytokinesFusion Proteins, bcr-ablpleiotrophinBone marrowHematologyLeukemiasStem cells

Identifiers

PMID31613796
PMCPMC6934217
OpenAlexW2981090231

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.