Imperial College London
Portrait Picture

DrNiklasFeldhahn

Faculty of Medicine, Department of Immunology and Inflammation

Senior Lecturer in Molecular Haematology
 
 
 
//

Contact

 

+44 (0)20 3313 1528n.feldhahn Website

 
 
//

Location

 

, 4N3DCommonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Sprangers:2006:10.1038/sj.onc.1209520,
author = {Sprangers, M and Feldhahn, N and Liedtke, S and Jumaa, H and Siebert, R and Muschen, M},
doi = {10.1038/sj.onc.1209520},
journal = {Oncogene},
pages = {5180--5186},
title = {SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells},
url = {http://dx.doi.org/10.1038/sj.onc.1209520},
volume = {25},
year = {2006}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Perpetual V(D)J recombinase activity involving multiple DNA double-strand break events in B-cell lineage leukemia and lymphoma cells may introduce secondary genetic aberrations leading towards malignant progression. Here, we investigated defective negative feedback signaling through the (pre-) B-cell receptor as a possible reason for deregulated V(D)J recombinase activity in B-cell malignancy. On studying 28 cases of pre-B-lymphoblastic leukemia and 27 B-cell lymphomas, expression of the (pre-) B-cell receptor-related linker molecule SLP65 (SH2 domain-containing lymphocyte protein of 65 kDa) was found to be defective in seven and five cases, respectively. SLP65 deficiency correlates with RAG1/2 expression and unremitting V(H) gene rearrangement activity. Reconstitution of SLP65 expression in SLP65-deficient leukemia and lymphoma cells results in downregulation of RAG1/2 expression and prevents both de novo V(H)-DJ(H) rearrangements and secondary V(H) replacement. We conclude that iterative V(H) gene rearrangement represents a frequent feature in B-lymphoid malignancy, which can be attributed to SLP65 deficiency in many cases.
AU  - Sprangers,M
AU  - Feldhahn,N
AU  - Liedtke,S
AU  - Jumaa,H
AU  - Siebert,R
AU  - Muschen,M
DO  - 10.1038/sj.onc.1209520
EP  - 5186
PY  - 2006///
SN  - 0950-9232
SP  - 5180
TI  - SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/sj.onc.1209520
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16636677
VL  - 25
ER  -
Download