Evidence map›Paper›PMID 27904138›Full record

ArticleLeukemia2017

Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.

J Yu, L Chen, B Cui, Christina Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf Ii, T J Kipps

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

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Review
  3. Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. The Roles of Secreted Wnt Ligands in Cancer.International journal of molecular sciences · 2023
    Review
  10. Review
  11. Review
  12. Wnt regulation of hematopoietic stem cell development and disease.Current topics in developmental biology · 2023
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. WNT Signaling as a Therapeutic Target for Glioblastoma.International journal of molecular sciences · 2021
    Review
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

10 authors at 1 institution in 1 country.

J YuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
L ChenMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
B CuiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Christina WuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
M Y ChoiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Y ChenMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
L ZhangMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
L Z RassentiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
G F Widhopf IiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
T J KippsMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
University of California, San Diego · US

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534
6 · The paper itself

Abstract

Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1

Indexed as

AdenineAnimalsAntibodies, MonoclonalApoptosisCell ProliferationHumansLeukemia, Lymphocytic, Chronic, B-CellMiceMice, SCIDPiperidinesPyrazolesPyrimidinesrac1 GTP-Binding ProteinReceptor Tyrosine Kinase-like Orphan ReceptorsTumor Cells, CulturedWnt-5a ProteinAdenineAntibodies, MonoclonalibrutinibPiperidinesPyrazolesPyrimidinesrac1 GTP-Binding ProteinRAC1 protein, humanReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanWnt-5a ProteinWNT5A protein, human

Identifiers

PMID27904138
PMCPMC5462858
OpenAlexW2559064918

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.