Imperial College London
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DrNiklasFeldhahn

Faculty of Medicine, Department of Immunology and Inflammation

Senior Lecturer in Molecular Haematology
 
 
 
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Contact

 

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

 
 
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Location

 

, 4N3DCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Klein:2006:10.1038/sj.onc.1209133,
author = {Klein, F and Feldhahn, N and Herzog, S and Sprangers, M and Mooster, JL and Jumaa, H and Muschen, M},
doi = {10.1038/sj.onc.1209133},
journal = {Oncogene},
pages = {1118--1124},
title = {BCR-ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells},
url = {http://dx.doi.org/10.1038/sj.onc.1209133},
volume = {25},
year = {2006}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pre-B lymphoblastic leukemia cells carrying a BCR-ABL1 gene rearrangement exhibit an undifferentiated phenotype. Comparing the genome-wide gene expression profiles of normal B-cell subsets and BCR-ABL1+ pre-B lymphoblastic leukemia cells by SAGE, the leukemia cells show loss of B lymphoid identity and aberrant expression of myeloid lineage-specific molecules. Consistent with this, BCR-ABL1+ pre-B lymphoblastic leukemia cells exhibit defective expression of IKAROS, a transcription factor needed for early lymphoid lineage commitment. As shown by inducible expression of BCR-ABL1 in human and murine B-cell precursor cell lines, BCR-ABL1 induces the expression of a dominant-negative IKAROS splice variant, termed IK6. Comparing matched leukemia sample pairs from patients before and during therapy with the BCR-ABL1 kinase inhibitor STI571 (Imatinib), inhibition of BCR-ABL1 partially corrected aberrant expression of IK6 and lineage infidelity of the leukemia cells. To elucidate the contribution of IK6 to lineage infidelity in BCR-ABL1+ cell lines, IK6 expression was silenced by RNA interference. Upon inhibition of IK6, BCR-ABL1+ leukemia cells partially restored B lymphoid lineage commitment. Therefore, we propose that BCR-ABL1 induces aberrant splicing of IKAROS, which interferes with lineage identity and differentiation of pre-B lymphoblastic leukemia cells.
AU  - Klein,F
AU  - Feldhahn,N
AU  - Herzog,S
AU  - Sprangers,M
AU  - Mooster,JL
AU  - Jumaa,H
AU  - Muschen,M
DO  - 10.1038/sj.onc.1209133
EP  - 1124
PY  - 2006///
SN  - 0950-9232
SP  - 1118
TI  - BCR-ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/sj.onc.1209133
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16205638
VL  - 25
ER  -
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