Evidence map›Paper›PMID 22387217›Full record

ArticleMolecular oncology2012

Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling.

Sangkil Nam, Anna Scuto, Fan Yang, Wenyong Chen, Sungman Park, Hwa-Seung Yoo, Heiko Konig, Ravi Bhatia, Xinlai Cheng, Karl-Heinz Merz and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Article
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  13. Review
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  15. Article
  16. Article
  17. Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid Leukemia Using a Network Pharmacology-Based Strategy.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  18. Article
  19. Article
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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

12 authors at 5 institutions in 3 countries.

Sangkil NamMolecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. snam@coh.org
Anna Scuto
Fan Yang
Wenyong Chen
Sungman Park
Hwa-Seung Yoo
Heiko Konig
Ravi Bhatia
Xinlai Cheng
Karl-Heinz Merz
Gerhard Eisenbrand
Richard Jove
City of Hope · USUniversity of Kaiserslautern · DEDaejeon University · KRJohns Hopkins University · USPenn State Milton S. Hershey Medical Center · US

Funding

Roles of SIRT1 in normal hematopoietic and leukemic stem cellsR01CA143421 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, WENYONG · 2011 to 2015
$1.5M
Inhibitors in Src Signaling for Antitumor TherapyR01CA115674 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI JOVE, RICHARD · 2007 to 2011
$1.4M
NCI NIH HHS R01 CA115674NCI NIH HHS R01 CA143421
6 · The paper itself

Abstract

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). While previous studies indicate that indirubin is a promising therapeutic agent for CML, the molecular mechanism of action of indirubin is not fully understood. We report here that indirubin derivatives (IRDs) potently inhibit Signal Transducer and Activator of Transcription 5 (Stat5) protein in CML cells. Compound E804, which is the most potent in this series of IRDs, blocked Stat5 signaling in human K562 CML cells, imatinib-resistant human KCL-22 CML cells expressing the T315I mutant Bcr-Abl (KCL-22M), and CD34-positive primary CML cells from patients. Autophosphorylation of Src family kinases (SFKs) was strongly inhibited in K562 and KCL-22M cells at 5 μM E804, and in primary CML cells at 10 μM E804, although higher concentrations partially inhibited autophosphorylation of Bcr-Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate downstream Stat5 signaling. Activation of Stat5 was strongly blocked by E804 in CML cells. E804 down-regulated expression of Stat5 target proteins Bcl-x(L) and Mcl-1, associated with induction of apoptosis. In sum, our findings identify IRDs as potent inhibitors of the SFK/Stat5 signaling pathway downstream of Bcr-Abl, leading to apoptosis of K562, KCL-22M and primary CML cells. IRDs represent a promising structural class for development of new therapeutics for wild type or T315I mutant Bcr-Abl-positive CML patients.

Indexed as

ApoptosisBenzamidesBlotting, WesternCell Line, TumorCell SurvivalElectrophoretic Mobility Shift AssayEnzyme InhibitorsHumansImatinib MesylateImmunoprecipitationIndolesK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveOximesPiperazinesPyridonesBenzamidesEnzyme InhibitorsImatinib MesylateindirubinIndirubin E804IndolesOximesPD 180970PiperazinesPyridonesPyrimidinesSTAT5 Transcription Factor

Identifiers

PMID22387217
PMCPMC3361532
OpenAlexW2111831547

What OpenQuestion holds

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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.