ArticleThe Journal of experimental medicine2004
Role of Dok-1 and Dok-2 in leukemia suppression.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 87 citations in OpenAlex.
- Plasma exosomal DOK3 reflects immunological states in lung tumor and predicts prognosis of gefitinib treatment.Cancer science · 2022Article
- Article
- Comprehensive analysis of DOK family genes expression, immune characteristics, and drug sensitivity in human tumors.Journal of advanced research · 2022Article
- DOK2 Has Prognostic and Immunologic Significance in Adults With Acute Myeloid Leukemia: A Novel Immune-Related Therapeutic Target.Frontiers in medicine · 2022Article
- Introduction to DOK2 and its potential role in cancer.Physiological research · 2021Review
- Hsa_Circ_0001947/MiR-661/DOK7 Axis Restrains Non-Small Cell Lung Cancer Development.Journal of microbiology and biotechnology · 2021Article
- Compound haploinsufficiency of Dok2 and Dusp4 promotes lung tumorigenesis.The Journal of clinical investigation · 2019Article
- Methylation-associated DOK1 and DOK2 down-regulation: Potential biomarkers for predicting adverse prognosis in acute myeloid leukemia.Journal of cellular physiology · 2018Article
- Purification of zebrafish erythrocytes as a means of identifying a novel regulator of haematopoiesis.British journal of haematology · 2018Article
- Dok-1 and Dok-2 Are Required To Maintain Herpes Simplex Virus 1-Specific CD8Journal of virology · 2017Article
- Turning the tide in myelodysplastic/myeloproliferative neoplasms.Nature reviews. Cancer · 2017Review
- Effects of expressing human T-cell leukemia virus type 1 (HTLV-I) oncoprotein Tax on DOK1, DOK2 and DOK3 gene expression in mice.The Journal of veterinary medical science · 2017Article
- The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase.BMC cancer · 2016Review
- Dok-1 negatively regulates platelet integrin αIIbβ3 outside-in signalling and inhibits thrombosis in mice.Thrombosis and haemostasis · 2016Article
- Article
- Mutational analysis of the DOK2 haploinsufficient tumor suppressor gene in chronic myelomonocytic leukemia (CMML).Leukemia · 2015Article
- Dok1 and Dok2 proteins regulate natural killer cell development and function.The EMBO journal · 2014Article
- mRNA expression of DOK1-6 in human breast cancer.World journal of clinical oncology · 2014Article
- Epstein-Barr virus down-regulates tumor suppressor DOK1 expression.PLoS pathogens · 2014Article
- Dok-2 adaptor protein regulates the shear-dependent adhesive function of platelet integrin αIIbβ3 in mice.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic myelogenous leukemia (CML) is characterized by the presence of the chimeric p210bcr/abl oncoprotein that shows elevated and constitutive protein tyrosine kinase activity relative to the normal c-abl tyrosine kinase. Although several p210bcr/abl substrates have been identified, their relevance in the pathogenesis of the disease is unclear. We have identified a family of proteins, Dok (downstream of tyrosine kinase), coexpressed in hematopoietic progenitor cells. Members of this family such as p62dok (Dok-1) and p56dok-2 (Dok-2) associate with the p120 rasGTPase-activating protein (rasGAP) upon phosphorylation by p210bcr/abl as well as receptor and nonreceptor tyrosine kinases. Here, we report the generation and characterization of single and double Dok-1 or Dok-2 knockout (KO) mutants. Single KO mice displayed normal steady-state hematopoiesis. By contrast, concomitant Dok-1 and Dok-2 inactivation resulted in aberrant hemopoiesis and Ras/MAP kinase activation. Strikingly, all Dok-1/Dok-2 double KO mutants spontaneously developed transplantable CML-like myeloproliferative disease due to increased cellular proliferation and reduced apoptosis. Furthermore, Dok-1 or Dok-2 inactivation markedly accelerated leukemia and blastic crisis onset in Tec-p210bcr/abl transgenic mice known to develop, after long latency, a myeloproliferative disorder resembling human CML. These findings unravel the critical and unexpected role of Dok-1 and Dok-2 in tumor suppression and control of the hematopoietic compartment homeostasis.
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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.