Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19).
In: Blood, Jg. 116 (2010-08-12), Heft 6, S. 962-70
Online
academicJournal
Zugriff:
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: | |
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: |
|
Sonstiges: |
|