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LMO2, a critical transcription regulator of hematopoiesis, is involved in human T-cell leukemia. The binding site of proline and acidic amino acid-rich protein (PAR) transcription factors in the promoter of the LMO2 gene plays a central role in hematopoietic-specific expression. E2A-HLF fusion derived from t(17;19) in B-precursor acute lymphoblastic leukemia (ALL) has the transactivation domain of E2A and the basic region/leucine zipper domain of HLF, which is a PAR transcription factor, raising the possibility that E2A-HLF aberrantly induces LMO2 expression. We here demonstrate that cell lines and a primary sample of t(17;19)-ALL expressed LMO2 at significantly higher levels than other B-precursor ALLs did. Transfection of E2A-HLF into a non-t(17;19) B-precursor ALL cell line induced LMO2 gene expression that was dependent on the DNA-binding and transactivation activities of E2A-HLF. The PAR site in the LMO2 gene promoter was critical for E2A-HLF-induced LMO2 expression. Gene silencing of LMO2 in a t(17;19)-ALL cell line by short hairpin RNA induced apoptotic cell death. These observations indicated that E2A-HLF promotes cell survival of t(17;19)-ALL cells by aberrantly up-regulating LMO2 expression. LMO2 could be a target for a new therapeutic modality for extremely chemo-resistant t(17;19)-ALL.

Titel:	Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19).
Autor/in / Beteiligte Person:	Hirose, K ; Inukai, T ; Kikuchi, J ; Furukawa, Y ; Ikawa, T ; Kawamoto, H ; Oram, SH ; Göttgens, B ; Kiyokawa, N ; Miyagawa, Y ; Okita, H ; Akahane, K ; Zhang, X ; Kuroda, I ; Honna, H ; Kagami, K ; Goi, K ; Kurosawa, H ; Look, AT ; Matsui, H ; Inaba, T ; Sugita, K
Link:	Full Text Finder (Volltext)
Zeitschrift:	Blood, Jg. 116 (2010-08-12), Heft 6, S. 962-70
Veröffentlichung:	2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2010
Medientyp:	academicJournal
ISSN:	1528-0020 (electronic)
DOI:	10.1182/blood-2009-09-244673
Schlagwort:	Adaptor Proteins, Signal Transducing Apoptosis physiology Blotting, Western Cell Line, Tumor Chromosomes, Human, Pair 17 Chromosomes, Human, Pair 19 Fetal Blood cytology Gene Expression Regulation, Leukemic Humans LIM Domain Proteins Lentivirus genetics Metalloproteins metabolism Oncogene Proteins, Fusion genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology Precursor Cells, B-Lymphoid cytology Promoter Regions, Genetic physiology Proto-Oncogene Proteins RNA, Small Interfering Transcription Factors genetics Up-Regulation genetics DNA-Binding Proteins genetics DNA-Binding Proteins metabolism Metalloproteins genetics Oncogene Proteins, Fusion metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics Precursor Cells, B-Lymphoid physiology Transcription Factors metabolism Translocation, Genetic
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Blood] 2010 Aug 12; Vol. 116 (6), pp. 962-70. <i>Date of Electronic Publication: </i>2010 Jun 02. MeSH Terms: Translocation, Genetic* ; DNA-Binding Proteins / genetics ; DNA-Binding Proteins / metabolism ; Metalloproteins / genetics ; Oncogene Proteins, Fusion / metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics ; Precursor Cells, B-Lymphoid / physiology ; Transcription Factors / *metabolism ; Adaptor Proteins, Signal Transducing ; Apoptosis / physiology ; Blotting, Western ; Cell Line, Tumor ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 19 ; Fetal Blood / cytology ; Gene Expression Regulation, Leukemic ; Humans ; LIM Domain Proteins ; Lentivirus / genetics ; Metalloproteins / metabolism ; Oncogene Proteins, Fusion / genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology ; Precursor Cells, B-Lymphoid / cytology ; Promoter Regions, Genetic / physiology ; Proto-Oncogene Proteins ; RNA, Small Interfering ; Transcription Factors / genetics ; Up-Regulation / genetics Grant Information: G0800784 United Kingdom MRC_ Medical Research Council; G0900729/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research Substance Nomenclature: 0 (Adaptor Proteins, Signal Transducing) ; 0 (DNA-Binding Proteins) ; 0 (E2a-Hlf fusion protein, human) ; 0 (LIM Domain Proteins) ; 0 (LMO2 protein, human) ; 0 (Metalloproteins) ; 0 (Oncogene Proteins, Fusion) ; 0 (Proto-Oncogene Proteins) ; 0 (RNA, Small Interfering) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20100604 Date Completed: 20100916 Latest Revision: 20211028 Update Code: 20240513

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Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19).