Evidence map›Paper›PMID 30254339›Full record

ArticleLeukemia2019

Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization.

Wei Liu, Wei Du, Xun Shang, Lei Wang, Chris Evelyn, Maria Carolina Florian, Marnie A Ryan, Ahmad Rayes, Xueheng Zhao, Kenneth Setchell and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025
    Review
  6. Article
  7. Article
  8. Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025
    Review
  9. Review
  10. Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Science advances · 2023
    Article
  18. Review
  19. Review
  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

16 authors at 4 institutions in 2 countries.

Wei Liu *Cancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Wei Du *Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, 26506, USA.ORCID http://orcid.org/0000-0003-3669-537X
Xun ShangCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Lei WangCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Chris EvelynCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Maria Carolina FlorianInstitute of Molecular Medicine, University of Ulm, Ulm, Germany.
Marnie A RyanCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Ahmad RayesCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Xueheng ZhaoDivision of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Kenneth SetchellDivision of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Jarek MellerDivision of Biomedical Informatics, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 45229, USA.
Fukun GuoCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Nicolas NassarCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Hartmut GeigerCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Qishen PangCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA.
Yi ZhengCancer and Blood Diseases Institute, University of Cincinnati, Cincinnati, OH, 45229, USA. yi.zheng@cchmc.org.
University of Cincinnati · USCincinnati Children's Hospital Medical Center · USUniversität Ulm · DEWest Virginia University · US

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Sally Lynn Hodder · 2012 to 2026
$81.0M
Leukemia stem cell polarity and differentiation therapyR01CA204895 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI MULLOY, JAMES C, ZHENG, YI · 2017 to 2021
$2.2M
Cdc42, hematopoietic stem cell polarity, and cell fateR01DK104814 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2016 to 2019
$2.0M
Cell Type and Stimulus-Specific Signaling Role of CDC42 in BloodR01HL085362 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2006 to 2010
$2.0M
Targeting Cdc42 for bone marrow transplant therapiesR01CA193350 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2015 to 2019
$1.8M
NCI NIH HHS R01 CA193350NCI NIH HHS R01 CA204895NHLBI NIH HHS R01 HL085362NIDDK NIH HHS R01 DK104814NIGMS NIH HHS U54 GM104942
6 · The paper itself

Abstract

Mobilization of hematopoietic stem cells (HSCs) from bone marrow (BM) to peripheral blood (PB) by cytokine granulocyte colony-stimulating factor (G-CSF) or the chemical antagonist of CXCR4, AMD3100, is important in the treatment of blood diseases. Due to clinical conditions of each application, there is a need for continued improvement of HSC mobilization regimens. Previous studies have shown that genetic ablation of the Rho GTPase Cdc42 in HSCs results in their mobilization without affecting survival. Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity and competitively interfere with guanine nucleotide exchange activity. CASIN inhibits intracellular Cdc42 activity specifically and transiently to induce murine hematopoietic stem/progenitor cell egress from the BM by suppressing actin polymerization, adhesion, and directional migration of stem/progenitor cells, conferring Cdc42 knockout phenotypes. We further show that, although, CASIN administration to mice mobilizes similar number of phenotypic HSCs as AMD3100, it produces HSCs with better long-term reconstitution potential than that by AMD3100. Our work validates a specific small molecule inhibitor for Cdc42, and demonstrates that signaling molecules downstream of cytokines and chemokines, such as Cdc42, constitute a useful target for long-term stem cell mobilization.

Indexed as

AnimalsBenzylaminesBone Marrowcdc42 GTP-Binding ProteinCell MovementCyclamsCytokinesGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell MobilizationHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHeterocyclic CompoundsMiceMice, Inbred C57BLSmall Molecule LibrariesStem CellsBenzylaminescdc42 GTP-Binding ProteinCdc42 protein, mouseCyclamsCytokinesGranulocyte Colony-Stimulating FactorHeterocyclic CompoundsplerixaforSmall Molecule Libraries

Identifiers

PMID30254339
PMCPMC6414073
OpenAlexW2889583223

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.