دورية أكاديمية
أعرض في EDS

Differential PAX5 levels promote malignant B-cell infiltration, progression and drug resistance, and predict a poor prognosis in MCL patients independent of CCND1.

التفاصيل البيبلوغرافية
العنوان: Differential PAX5 levels promote malignant B-cell infiltration, progression and drug resistance, and predict a poor prognosis in MCL patients independent of CCND1.
المؤلفون: Teo AE; Center for Stem Cell and Regenerative Medicine, Brown Foundation, Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), University of Texas-Health Science Center at Houston, Houston, TX, USA., Chen Z; Center for Stem Cell and Regenerative Medicine, Brown Foundation, Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), University of Texas-Health Science Center at Houston, Houston, TX, USA., Miranda RN; Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., McDonnell T; Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Medeiros LJ; Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., McCarty N; Center for Stem Cell and Regenerative Medicine, Brown Foundation, Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), University of Texas-Health Science Center at Houston, Houston, TX, USA.
المصدر: Leukemia [Leukemia] 2016 Mar; Vol. 30 (3), pp. 580-93. Date of Electronic Publication: 2015 May 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : London : Nature Publishing Group, Specialist Journals
Original Publication: [Baltimore, Md.] : Williams & Wilkins, [c1987-
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic*, B-Lymphocytes/*metabolism , Drug Resistance, Neoplasm/*genetics , Lymphoma, Mantle-Cell/*genetics , PAX5 Transcription Factor/*genetics, Animals ; Antineoplastic Agents/pharmacology ; B-Lymphocytes/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cyclin D1/genetics ; Cyclin D1/metabolism ; High-Throughput Screening Assays ; Humans ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lymphoma, Mantle-Cell/diagnosis ; Lymphoma, Mantle-Cell/drug therapy ; Lymphoma, Mantle-Cell/mortality ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/pathology ; Mice ; PAX5 Transcription Factor/antagonists & inhibitors ; PAX5 Transcription Factor/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Xenograft Model Antitumor Assays
مستخلص: Reduced Paired box 5 (PAX5) levels have important roles in the pathogenesis of human B-cell acute lymphoblastic leukemia. However, the role of PAX5 in human lymphoma remains unclear. We generated PAX5-silenced cells using mantle cell lymphoma (MCL) as a model system. These PAX5(-) MCL cells exhibited unexpected phenotypes, including increased proliferation in vitro, enhanced tumor infiltration in vivo, robust adhesion to the bone marrow stromal cells and increased retention of quiescent stem-like cells. These phenotypes were attributed to alterations in the expression of genes including p53 and Rb, and to phosphoinositide 3-kinase/mammalian target of rapamycin and phosphorylated signal transducer and activator of transcription 3 pathway hyperactivation. On PAX5 silencing, the MCL cells displayed upregulated interleukin (IL)-6 expression and increased responses to paracrine IL-6. Moreover, decreased PAX5 levels in CD19+ MCL cells correlated with their increased infiltration and progression; thus, PAX5 levels can be used as a prognostic marker independent of cyclin D1 in advanced MCL patients. Importantly, high-throughput screening of 3800 chemical compounds revealed that PAX5(-) MCL cells are highly drug-resistant compared with PAX5 wild-type MCL cells. Collectively, the results of our study support a paradigm shift regarding the functions of PAX5 in human B-cell cancer and encourage future efforts to design effective therapies against MCL.
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معلومات مُعتمدة: R01 CA181319 United States CA NCI NIH HHS; UL1 TR000371 United States TR NCATS NIH HHS
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (CCND1 protein, human)
0 (IL6 protein, human)
0 (Interleukin-6)
0 (PAX5 Transcription Factor)
0 (PAX5 protein, human)
0 (Retinoblastoma Protein)
0 (STAT3 Transcription Factor)
0 (STAT3 protein, human)
0 (Tumor Suppressor Protein p53)
136601-57-5 (Cyclin D1)
EC 2.7.1.1 (MTOR protein, human)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20150616 Date Completed: 20160719 Latest Revision: 20211203
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4644730
DOI: 10.1038/leu.2015.140
PMID: 26073757
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5551
DOI:10.1038/leu.2015.140