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| Home > Publications database > The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL. > print |
| 001 | 127693 | ||
| 005 | 20240228140944.0 | ||
| 024 | 7 | _ | |a 10.1038/leu.2015.114 |2 doi |
| 024 | 7 | _ | |a pmid:25936528 |2 pmid |
| 024 | 7 | _ | |a 0887-6924 |2 ISSN |
| 024 | 7 | _ | |a 1476-5551 |2 ISSN |
| 024 | 7 | _ | |a altmetric:4019924 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2017-03716 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Vasyutina, E. |b 0 |
| 245 | _ | _ | |a The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL. |
| 260 | _ | _ | |a Basingstoke |c 2015 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1521721971_2108 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Dysregulated T-cell leukemia/lymphoma-1A (TCL1A), a modulator in B-cell receptor (BCR) signaling, is causally implicated in chronic lymphocytic leukemia (CLL). However, the mechanisms of the perturbed TCL1A regulation are largely unknown. To characterize TCL1A-upstream networks, we functionally screened for TCL1A-repressive micro-RNAs (miRs) and their transcriptional regulators. We identified the novel miR-484 to target TCL1As 3-UTR and to be downregulated in CLL. In chromatin immunoprecipitations and reporter assays, the oncogenic transcription factor of myeloid cells, EVI1, bound and activated the miR-484 promoter. Most common in CLL was a pan-EVI1 transcript variant. EVI1 protein expression revealed distinct normal-tissue and leukemia-associated patterns of EVI1/TCL1A co-regulation. EVI1 levels were particularly low in TCL1A-high CLL or such cellular subsets. Global gene expression profiles from a 337-patient set linked EVI1 networks to BCR signaling and cell survival via TCL1A, BTK and other molecules of relevance in CLL. Enforced EVI1, as did miR-484, repressed TCL1A. Furthermore, it reduced phospho-kinase levels, impaired cell survival, mitigated BCR-induced Ca-flux and diminished the in vitro ibrutinib response. Moreover, TCL1A and EVI1 showed a strongly interactive hazard prediction in prospectively treated patients. Overall, we present regressive EVI1 as a novel regulatory signature in CLL. Through enhanced TCL1A and other EVI1-targeted hallmarks of CLL, this contributes to an aggressive cellular and clinical phenotype. |
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| 650 | _ | 7 | |a Biomarkers, Tumor |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA-Binding Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a MECOM protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a MIRN484 microRNA, human |2 NLM Chemicals |
| 650 | _ | 7 | |a MicroRNAs |2 NLM Chemicals |
| 650 | _ | 7 | |a Proto-Oncogene Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA, Messenger |2 NLM Chemicals |
| 650 | _ | 7 | |a TCL1A protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Transcription Factors |2 NLM Chemicals |
| 700 | 1 | _ | |a Boucas, J. M. |b 1 |
| 700 | 1 | _ | |a Bloehdorn, J. |b 2 |
| 700 | 1 | _ | |a Aszyk, C. |b 3 |
| 700 | 1 | _ | |a Crispatzu, G. |b 4 |
| 700 | 1 | _ | |a Stiefelhagen, M. |b 5 |
| 700 | 1 | _ | |a Breuer, A. |b 6 |
| 700 | 1 | _ | |a Mayer, P. |b 7 |
| 700 | 1 | _ | |a Lengerke, C. |b 8 |
| 700 | 1 | _ | |a Döhner, H. |b 9 |
| 700 | 1 | _ | |a Beutner, D. |b 10 |
| 700 | 1 | _ | |a Rosenwald, A. |b 11 |
| 700 | 1 | _ | |a Stilgenbauer, S. |b 12 |
| 700 | 1 | _ | |a Hallek, M. |b 13 |
| 700 | 1 | _ | |a Benner, A. |0 P:(DE-He78)e15dfa1260625c69d6690a197392a994 |b 14 |u dkfz |
| 700 | 1 | _ | |a Herling, M. |b 15 |
| 773 | _ | _ | |a 10.1038/leu.2015.114 |g Vol. 29, no. 10, p. 2003 - 2014 |0 PERI:(DE-600)2008023-2 |n 10 |p 2003 - 2014 |t Leukemia |v 29 |y 2015 |x 1476-5551 |
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