دورية أكاديمية
Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute lymphoblastic leukemia.
العنوان: | Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute lymphoblastic leukemia. |
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المؤلفون: | Linger RM; Department of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplantation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Lee-Sherick AB, DeRyckere D, Cohen RA, Jacobsen KM, McGranahan A, Brandão LN, Winges A, Sawczyn KK, Liang X, Keating AK, Tan AC, Earp HS, Graham DK |
المصدر: | Blood [Blood] 2013 Aug 29; Vol. 122 (9), pp. 1599-609. Date of Electronic Publication: 2013 Jul 16. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
مواضيع طبية MeSH: | Molecular Targeted Therapy*, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy , Proto-Oncogene Proteins/*antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors, Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Gene Expression Regulation, Leukemic/drug effects ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA, Small Interfering/pharmacology ; RNA, Small Interfering/therapeutic use ; Xenograft Model Antitumor Assays ; c-Mer Tyrosine Kinase |
مستخلص: | Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications. |
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معلومات مُعتمدة: | K12-HD000850 United States HD NICHD NIH HHS; R01CA137078 United States CA NCI NIH HHS; CA98543 United States CA NCI NIH HHS; P30CA046934 United States CA NCI NIH HHS; U24 CA114766 United States CA NCI NIH HHS; K12 HD000850 United States HD NICHD NIH HHS; R01 CA137078 United States CA NCI NIH HHS; U10 CA098543 United States CA NCI NIH HHS; CA114766 United States CA NCI NIH HHS; P30 CA016086 United States CA NCI NIH HHS; T32 CA082086 United States CA NCI NIH HHS; P30 CA046934 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Proto-Oncogene Proteins) 0 (RNA, Small Interfering) EC 2.7.10.1 (MERTK protein, human) EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) EC 2.7.10.1 (c-Mer Tyrosine Kinase) |
تواريخ الأحداث: | Date Created: 20130718 Date Completed: 20131203 Latest Revision: 20220408 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC3757372 |
DOI: | 10.1182/blood-2013-01-478156 |
PMID: | 23861246 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1528-0020 |
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DOI: | 10.1182/blood-2013-01-478156 |