English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation

Marneth, A. E., Prange, K. H. M., Al Hinai, A. S. A., Bergevoet, S. M., Tesi, N., Janssen-Megens, E. M., et al. (2017). C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation. Leukemia: the Journal of Normal and Malignant Hemopoiese; Official Journal of the Leukemia Research Fund U.K., 2017, 1-9. doi:10.1038/leu.2017.280.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BC55-D Version Permalink: http://hdl.handle.net/21.11116/0000-0000-BC56-C
Genre: Journal Article

Files

show Files
hide Files
:
Marneth.pdf (Publisher version), 2MB
Name:
Marneth.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2017 Macmillan Publishers Limited, part of Springer Nature
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Marneth, A. E., Author
Prange, K. H. M., Author
Al Hinai, A. S. A., Author
Bergevoet, S. M., Author
Tesi, N., Author
Janssen-Megens, E. M., Author
Kim, B., Author
Sharifi, N., Author
Yaspo, M. L.1, Author              
Kuster, J., Author
Sanders, M. A., Author
Stoetman, E. C. G., Author
Knijnenburg, J., Author
Arentsen-Peters, Tcjm, Author
Zwaan, C. M., Author
Stunnenberg, H. G., Author
van den Heuvel-Eibrink, M. M., Author
Haferlach, T., Author
Fornerod, M., Author
Jansen, J. H., Author
Valk, P. J. M., Authorvan der Reijden, B. A., AuthorMartens, J. H. A., Author more..
Affiliations:
1Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              

Content

show
hide
Free keywords: -
 Abstract: Overexpression of the BRE (brain and reproductive organ-expressed) gene defines a distinct pediatric and adult acute myeloid leukemia (AML) subgroup. Here we identify a promoter enriched for active chromatin marks in BRE intron 4 causing strong biallelic expression of a previously unknown C-terminal BRE transcript. This transcript starts with BRE intron 4 sequences spliced to exon 5 and downstream sequences, and if translated might code for an N terminally truncated BRE protein. Remarkably, the new BRE transcript was highly expressed in over 50% of 11q23/KMT2A (lysine methyl transferase 2A)-rearranged and t(8;16)/KAT6A-CREBBP cases, while it was virtually absent from other AML subsets and normal tissues. In gene reporter assays, the leukemia-specific fusion protein KMT2A-MLLT3 transactivated the intragenic BRE promoter. Further epigenome analyses revealed 97 additional intragenic promoter marks frequently bound by KMT2A in AML with C-terminal BRE expression. The corresponding genes may be part of a context-dependent KMT2A-MLLT3-driven oncogenic program, because they were higher expressed in this AML subtype compared with other groups. C-terminal BRE might be an important contributor to this program because in a case with relapsed AML, we observed an ins(11;2) fusing CHORDC1 to BRE at the region where intragenic transcription starts in KMT2A-rearranged and KAT6A-CREBBP AML.Leukemia advance online publication, 24 October 2017; doi:10.1038/leu.2017.280.

Details

show
hide
Language(s): eng - English
 Dates: 2017-08-102017-09-05
 Publication Status: Published online
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/leu.2017.280
ISSN: 1476-5551 (Electronic)0887-6924 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Leukemia : the Journal of Normal and Malignant Hemopoiese ; Official Journal of the Leukemia Research Fund U.K.
  Other : Leukemia (Online-Ausg.)
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Basingstoke : Nature Publ. Group
Pages: - Volume / Issue: 2017 Sequence Number: - Start / End Page: 1 - 9 Identifier: ISSN: 0887-6924
CoNE: https://pure.mpg.de/cone/journals/resource/954925554401