Evidence map›Paper›PMID 22552008›Full record

ArticleLeukemia2012

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.

A Lopez-Girona, D Mendy, T Ito, K Miller, A K Gandhi, J Kang, S Karasawa, G Carmel, P Jackson, M Abbasian and 10 more

Erratum issued Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05199311 (A Phase I/II Study of Carfilzomib, Iberdomide), which is not on this map. Cited by 409 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
409citing papers in PubMed, 1 pooled it
22.1field-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.

NCT05199311 phase1 / phase2suspendednot on this mapstarted 2022, after this paper: background citation

A Phase I/II Study of Carfilzomib, Iberdomide (CC-220) and Dexamethasone (KID) in Patients With Newly Diagnosed Transplant Eligible Multiple Myeloma

TypeinterventionalSponsorHackensack Meridian HealthRan2022 to 2027Enrolled66ConditionsMultiple MyelomaArmsCarfilzomib, Iberdomide, Oral Dexamethasone
3 · Its place in the literature

Who cites it

409 citing papers in PubMed, 1 synthesis or guideline pooled it, 790 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  6. Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
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  8. Trial
  9. Trial
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  13. Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

349 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

20 authors at 2 institutions in 2 countries.

A Lopez-GironaCelgene, San Diego, CA 92121, USA. alopez@celgene.com
D Mendy
T Ito
K Miller
A K Gandhi
J Kang
S Karasawa
G Carmel
P Jackson
M Abbasian
A Mahmoudi
B Cathers
E Rychak
S Gaidarova
R Chen
P H Schafer
H Handa
T O Daniel
J F Evans
R Chopra
Tokyo Institute of Technology · JPBristol-Myers Squibb (Switzerland) · CH

Funding

Cancer Research UK 11566
6 · The paper itself

Abstract

Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. Our biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomide and pomalidomide.

Indexed as

Adaptor Proteins, Signal TransducingAdjuvants, ImmunologicAntineoplastic AgentsHEK293 CellsHumansLenalidomidePeptide HydrolasesThalidomideUbiquitinationUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingAdjuvants, ImmunologicAntineoplastic AgentsCRBN protein, humanLenalidomidePeptide HydrolasespomalidomideThalidomideUbiquitin-Protein Ligases

Identifiers

PMID22552008
PMCPMC3496085
OpenAlexW2066713758

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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.