| | |  | | | | Record from Web of Science® | | | | | | |
| Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor |
|
|
| Author(s): Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, Laken SJ, Kastan MB, Look AT |
| Source: NATURE Volume: 382 Issue: 6591 Pages: 541-544 Published: AUG 8 1996 |
| Times Cited: 99 References: 26 |
| Abstract: THE E2A-HLF (for hepatic leukaemia factor) fusion gene, formed by action of the t(17;19) (q22;p13) chromosomal translocation, drives the leukaemic transformation of early B-cell precursors(1-4), but the mechanism of this activity remains unknown. Here we report that human leukaemia cells carrying the translocation t(17;19) rapidly died by apoptosis when programmed to express a dominant-negative suppressor of the fusion protein E2A-HLF, indicating that the chimaeric oncoprotein probably affects cell survival rather than cell growth. Moreover, when introduced into murine pro-B lymphocytes, the oncogenic E2A-HLF fusion protein reversed both interleukin-3-dependent and p53-mediated apoptosis. The close homology of the basic region/leucine zipper (bZIP) DNA-binding and dimerization domain of HLF to that of the CES-2 cell death specification protein of Caenorhabditis elegans(5) suggests a model of leukaemogenesis in which E2A-HLF blocks an early step within an evolutionarily conserved cell-death pathway(6-9). |
| Document Type: Article |
| Language: English |
Addresses:
1. ST JUDE CHILDRENS HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38105 USA
2. UNIV TENNESSEE, COLL MED, DEPT PEDIAT, MEMPHIS, TN 38163 USA
3. JOHNS HOPKINS ONCOL CTR, BALTIMORE, MD 21287 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: VB258 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |