Evidence map›Paper›PMID 12024032›Full record

ArticleMolecular and cellular biology2002

Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis.

Artur Slupianek, Grazyna Hoser, Ireneusz Majsterek, Agnieszka Bronisz, Maciej Malecki, Janusz Blasiak, Richard Fishel, Tomasz Skorski

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

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
5.4field-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

72 citing papers in PubMed, 204 citations in OpenAlex.

  1. Trial
  2. Trial
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  4. Styrylquinazoline derivatives as ABL inhibitors selective for different DFG orientations.Journal of enzyme inhibition and medicinal chemistry · 2023
    Article
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  19. RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  20. Article

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

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

8 authors at 4 institutions in 3 countries.

Artur SlupianekCenter for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Grazyna Hoser
Ireneusz Majsterek
Agnieszka Bronisz
Maciej Malecki
Janusz Blasiak
Richard Fishel
Tomasz Skorski
Temple University · USInstitute for Postgraduate Medical Education · CZSidney Kimmel Cancer Center · USUniversity of Łódź · PL

Funding

Role of STATs in BCR/ABL induced leukemiasR01CA089052 · NCI · TEMPLE UNIVERSITY · PI SKORSKI, TOMASZ · 2001 to 2005
$1.4M
NCI NIH HHS CA89052NCI NIH HHS R01 CA089052
6 · The paper itself

Abstract

Fusion tyrosine kinases (FTKs) such as BCR/ABL, TEL/ABL, TEL/JAK2, TEL/PDGF beta R, TEL/TRKC(L), and NPM/ALK arise from reciprocal chromosomal translocations and cause acute and chronic leukemias and non-Hodgkin's lymphoma. FTK-transformed cells displayed drug resistance against the cytostatic drugs cisplatin and mitomycin C. These cells were not protected from drug-mediated DNA damage, implicating activation of the mechanisms preventing DNA damage-induced apoptosis. Various FTKs, except TEL/TRKC(L), can activate STAT5, which may be required to induce drug resistance. We show that STAT5 is essential for FTK-dependent upregulation of RAD51, which plays a central role in homology-dependent recombinational repair (HRR) of DNA double-strand breaks (DSBs). Elevated levels of Rad51 contributed to the induction of drug resistance and facilitation of the HRR in FTK-transformed cells. In addition, expression of antiapoptotic protein Bcl-xL was enhanced in cells transformed by the FTKs able to activate STAT5. Moreover, cells transformed by all examined FTKs displayed G(2)/M delay upon drug treatment. Individually, elevated levels of Rad51, Bcl-xL, or G(2)/M delay were responsible for induction of a modest drug resistance. Interestingly, combination of these three factors in nontransformed cells induced drug resistance of a magnitude similar to that observed in cells expressing FTKs activating STAT5. Thus, we postulate that RAD51-dependent facilitation of DSB repair, antiapoptotic activity of Bcl-xL, and delay in progression through the G(2)/M phase work in concert to induce drug resistance in FTK-positive leukemias and lymphomas.

Indexed as

Recombination, GeneticAnimalsApoptosisbcl-X ProteinCell Transformation, NeoplasticDNA-Binding ProteinsDNA RepairDrug ResistanceETS Translocation Variant 6 ProteinFusion Proteins, bcr-ablG2 PhaseHumansJanus Kinase 2LeukemiaMiceMice, Inbred C57BLBCL2L1 protein, humanBcl2l1 protein, mousebcl-X ProteinDNA-Binding ProteinsETS Translocation Variant 6 ProteinFusion Proteins, bcr-ablJanus Kinase 2Oncogene Proteins, Fusionp80(NPM-ALK) proteinProtein-Tyrosine KinasesProto-Oncogene Proteins c-bcl-2RAD51 protein, humanRad51 protein, mouseRad51 RecombinaseTEL-ABL fusion protein, humanTEL-JAK2 fusion protein, humanTEL-JAK2 fusion protein, mouseTEL-PDGFRbeta fusion protein, humanTEL-TRKC fusion protein, human

Identifiers

PMID12024032
PMCPMC133854
OpenAlexW2165848530

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.