Academic Journal
Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression.
| العنوان: | Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression. |
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| المؤلفون: | Baron, Frédéric, Turhan, Ali G, Giron-Michel, Julien, Azzarone, Bruno, Bentires-Alj, Mohamed, Bours, Vincent, Bourhis, Jean Henri, Chouaib, Salem, Caignard, Anne |
| المصدر: | Blood, 99 (6), 2107-13 (2002) |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2002 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | Antigens, CD34, Cell Differentiation, Cytotoxicity, Immunologic/drug effects/immunology, Fetal Blood/cytology, Fusion Proteins, bcr-abl/genetics/metabolism/pharmacology, Hematopoietic Stem Cells/cytology, Humans, Intercellular Adhesion Molecule-1/drug effects/immunology/metabolism, Killer Cells, Natural/cytology/immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology/pathology, NF-kappa B/immunology/metabolism/pharmacology, Transfection, Tumor Cells, Cultured, Life sciences, Genetics & genetic processes, Sciences du vivant, Génétique & processus génétiques |
| الوصف: | peer reviewed ; Chronic myeloid leukemia is a clonal myeloproliferative expansion of transformed primitive hematopoietic progenitor cells characterized by high-level expression of BCR-ABL chimeric gene, which induces growth factor independence. However, the influence of BCR-ABL expression on cell-mediated cytotoxicity is poorly understood. In the present study, we asked whether BCR-ABL expression interferes with leukemic target sensitivity to natural killer (NK) cell cytolysis. Our approach was based on the use of 2 BCR-ABL transfectants of the pluripotent hematopoietic cell line UT-7 expressing low (UT-7/E8, UT-7/G6) and high (UT-7/9) levels of BCR-ABL. As effector cells, we used CD56(bright), CD16-, CD2- NK cells differentiated in vitro from CD34 cord blood progenitors. We demonstrated that BCR-ABL transfectants UT-7/9 were lysed by NK cells with a higher efficiency than parental and low UT-7/E8.1 and UT-7/G6 transfectants. This enhanced susceptibility to lysis correlated with an increase in expression of intercellular adhesion molecule 1 (ICAM-1) by target cells. Treatment of UT-7/9 cells by STI571 (a specific inhibitor of the abl kinase) resulted in a decrease in NK susceptibility to lysis and ICAM-1 down-regulation in target cells. Furthermore, the constitutive activation of nuclear factor-kappaB (NF-kappaB) detected in BCR-ABL transfectant UT-7/9, was significantly attenuated when cells were treated by STI571. Interestingly, inhibition of NF-kappaB activation by BAY11-67082 (a specific NF-kappaB inhibitor) resulted in down-regulation of ICAM-1 expression and a subsequent decrease in NK-induced killing of UT-7/9 transfectants. Our results show that oncogenic transformation by BCR-ABL may increase susceptibility of leukemic progenitors to NK cell cytotoxicity by a mechanism involving overexpression of ICAM-1 as a consequence of NF-kappaB activation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0006-4971 1528-0020 |
| Relation: | urn:issn:0006-4971; urn:issn:1528-0020; https://orbi.uliege.be/handle/2268/83939; info:hdl:2268/83939; info:pmid:11877286 |
| DOI: | 10.1182/blood.V99.6.2107 |
| الاتاحة: | https://orbi.uliege.be/handle/2268/83939 https://doi.org/10.1182/blood.V99.6.2107 |
| Rights: | restricted access ; http://purl.org/coar/access_right/c_16ec ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.F7BBBB31 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00064971 15280020 |
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| DOI: | 10.1182/blood.V99.6.2107 |