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{Kaur:2007:10.1186/1476-4598-6-67,
author = {Kaur, P and Feldhahn, N and Zhang, B and Trageser, D and Muschen, M and Pertz, V and Groffen, J and Heisterkamp, N},
doi = {10.1186/1476-4598-6-67},
journal = {Mol Cancer},
title = {Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia},
url = {http://dx.doi.org/10.1186/1476-4598-6-67},
volume = {6},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Ph-positive leukemias are caused by the aberrant fusion of the BCR and ABL genes. Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor related to imatinib, which is widely used to treat chronic myelogenous leukemia. Because Ph-positive acute lymphoblastic leukemia only responds transiently to imatinib therapy, we have used mouse models to test the efficacy of nilotinib against lymphoblastic leukemia caused by the P190 form of Bcr/Abl. RESULTS: After transplant of 10,000 highly malignant leukemic cells into compatible recipients, untreated mice succumbed to leukemia within 21 days, whereas mice treated with 75 mg/kg nilotinib survived significantly longer. We examined cells from mice that developed leukemia while under treatment for Bcr/Abl kinase domain point mutations but these were not detected. In addition, culture of such cells ex vivo showed that they were as sensitive as the parental cell line to nilotinib but that the presence of stromal support allowed resistant cells to grow out. Nilotinib also exhibited impressive anti-leukemia activity in P190 Bcr/Abl transgenic mice that had developed overt leukemia/lymphoma masses and that otherwise would have been expected to die within 7 days. Visible lymphoma masses disappeared within six days of treatment and leukemic cell numbers in peripheral blood were significantly reduced. Treated mice survived more than 30 days. CONCLUSION: These results show that nilotinib has very impressive anti-leukemia activity but that lymphoblastic leukemia cells can become unresponsive to it both in vitro and in vivo through mechanisms that appear to be Bcr/Abl independent.
AU  - Kaur,P
AU  - Feldhahn,N
AU  - Zhang,B
AU  - Trageser,D
AU  - Muschen,M
AU  - Pertz,V
AU  - Groffen,J
AU  - Heisterkamp,N
DO  - 10.1186/1476-4598-6-67
PY  - 2007///
SN  - 1476-4598
TI  - Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia
T2  - Mol Cancer
UR  - http://dx.doi.org/10.1186/1476-4598-6-67
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17958915
VL  - 6
ER  -
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