ArticleProceedings of the National Academy of Sciences of the United States of America2007
Retroviral insertional mutagenesis identifies RUNX genes involved in chronic myeloid leukemia disease persistence under imatinib treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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.
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.
Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- AMPK-induced novel phosphorylation of RUNX1 inhibits STAT3 activation and overcome imatinib resistance in chronic myelogenous leukemia (CML) subjects.Cell death discovery · 2023Article
- Article
- Article
- RUNX family: Oncogenes or tumor suppressors (Review).Oncology reports · 2019Review
- UnPAKing RUNX3 functions-Both sides of the coin.Small GTPases · 2019Review
- FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance.International journal of hematology · 2013Review
- Review
- Fas-associated phosphatase 1 mediates Fas resistance in myeloid progenitor cells expressing the Bcr-abl oncogene.Leukemia & lymphoma · 2013Article
- Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics.BMC cancer · 2013Article
- Article
- Genetic mechanisms of chronic myeloid leukemia blastic transformation.Current hematologic malignancy reports · 2012Review
- RUNX3 is involved in caspase-3-dependent apoptosis induced by a combination of 5-aza-CdR and TSA in leukaemia cell lines.Journal of cancer research and clinical oncology · 2012Article
- CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression.The Journal of clinical investigation · 2012Article
- In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease.Leukemia · 2011Article
- A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases.Leukemia · 2011Article
- Chronic myeloid leukemia cells refractory/resistant to tyrosine kinase inhibitors are genetically unstable and may cause relapse and malignant progression to the terminal disease state.Leukemia & lymphoma · 2011Review
- Runx regulation of sphingolipid metabolism and survival signaling.Cancer research · 2010Article
- Chronic myeloid leukemia: mechanisms of blastic transformation.The Journal of clinical investigation · 2010Review
- Review
- Predictors of primary imatinib resistance in chronic myelogenous leukemia are distinct from those in secondary imatinib resistance.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kinase inhibitor imatinib mesylate targeting the oncoprotein Bcr-Abl has revolutionized the treatment of chronic myeloid leukemia (CML). However, even though imatinib successfully controls the leukemia in chronic phase, it seems not to be able to cure the disease, potentially necessitating lifelong treatment with the inhibitor under constant risk of relapse. On a molecular level, the cause of disease persistence is not well understood. Initial studies implied that innate features of primitive progenitor cancer stem cells may be responsible for the phenomenon. Here, we describe an assay using retroviral insertional mutagenesis (RIM) to identify genes contributing to disease persistence in vivo. We transplanted mice with bone marrow cells retrovirally infected with the Bcr-Abl oncogene and subsequently treated the animals with imatinib to select for leukemic cells in which the proviral integration had affected genes modulating the imatinib response. Southern blot analysis demonstrated clonal outgrowth of cells carrying similar integration sites. Candidate genes located near the proviral insertion sites were identified, among them the transcription factor RUNX3. Proviral integration near the RUNX3 promoter induced RUNX3 expression, and Bcr-Abl-positive cell lines with stable or inducible expression of RUNX1 or RUNX3 were protected from imatinib-induced apoptosis. Furthermore, imatinib treatment selected for RUNX1-expressing cells in vitro and in vivo after infection of primary bone marrow cells with Bcr-Abl and RUNX1. Our results demonstrate the utility of RIM for probing molecular modulators of targeted therapies and suggest a role for members of the RUNX transcription factor family in disease persistence in CML patients.
Indexed as
Identifiers
What OpenQuestion holds
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.