Constitutive NF-kappab/Rel activation in philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)
| Autor: | Oliver G. Ottmann, Dieter Kirchner, Roland M. Schmid, Gerd Munzert, Lothar Bergmann |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Oncogene Proteins v-rel Fusion Proteins bcr-abl Chromosomal translocation Apoptosis Nerve Tissue Proteins X-Linked Inhibitor of Apoptosis Protein IκB kinase Biology Protein Serine-Threonine Kinases Inhibitor of Apoptosis Proteins hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive Transcriptional regulation medicine Humans RNA Messenger RNA Neoplasm Tumor Necrosis Factor alpha-Induced Protein 3 Regulation of gene expression Kinase Reverse Transcriptase Polymerase Chain Reaction I-Kappa-B Kinase Intracellular Signaling Peptides and Proteins NF-kappa B Nuclear Proteins Proteins Forkhead Transcription Factors Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease TNF Receptor-Associated Factor 2 TNF Receptor-Associated Factor 1 XIAP I-kappa B Kinase DNA-Binding Proteins Gene Expression Regulation Neoplastic Leukemia Oncology Cancer research |
| Zdroj: | Leukemialymphoma. 45(6) |
| ISSN: | 1042-8194 |
| Popis: | The Bcr-Abl translocation t(9;22)(q34;q11 ) defines a subgroup of ALL patients with a dismal prognosis despite the introduction of intensified induction and consolidation regimen. Although Bcr-Abl induced NF-kappaB/Rel activation has previously been shown, the role of NF-kappaB/Rel in Ph+ leukemia is unclear. Using DNA binding assays, we demonstrate constitutive NF-kappaB/Rel activity in nuclear extracts from Ph+ ALL blasts, whereas Ph- primary blast cells and B-precursor cell lines lack NF-kappaB/Rel activity. NF-kappaB/Rel activity was shown in the ela2 and the b2a2 subtypes. Constitutive NF-kappaB/Rel activity in Ph+ blasts is not due to elevated endogenous IkappaB kinase (IKK) activity as shown by immune complex kinase assays. Since NF-kappaB/Rel is a transcriptional regulator of inhibitors of apoptosis we examined the expression of anti-apoptotic genes known to be induced by NF-kappaB/Rel by real time PCR analysis. We found no induction of TRAFI, TRAF2, cIAPI, cIAP2, XIAP, A20 or Bfl/Al in Ph+ ALL samples as compared to Ph-negative ALL controls. In summary, constitutive NF-kappaB/Rel activation independent of endogenous IKK activation may be a common finding in Ph+ ALL. However, targets of NF-kappaB/Rel mediated transcriptional regulation in this disease remain to be identified. |
| Databáze: | OpenAIRE |
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