PMID- 18194453
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20220114
IS  - 1582-1838 (Print)
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Linking)
VI  - 12
IP  - 5B
DP  - 2008 Oct
TI  - Nilotinib hampers the proliferation and function of CD8+ T lymphocytes through 
      inhibition of T cell receptor signalling.
PG  - 2107-18
LID - 10.1111/j.1582-4934.2008.00234.x [doi]
AB  - The novel selective BCR-ABL Breakpoint cluster region--Abelson murine leukemia 
      viral oncogene homolog 1 (BCR-AML) inhibitor nilotinib (AMN107) is a tyrosine 
      kinase inhibitor that is more potent against leukaemia cells in vitro than 
      imatinib. As nilotinib might be used in the context of allogeneic stem cell 
      transplantation where CD8+ T lymphocytes play a pivotal role in the 
      graft-versus-leukaemia (GVL) effect, we investigated effects of nilotinib on this 
      lymphocyte subpopulation. Nilotinib inhibits phytohemagglutinin (PHA)-induced 
      proliferation of CD8+T lymphocytes in vitro at therapeutically relevant 
      concentrations (0.5-4 microM). The inhibition of CD8+ T lymphocytes specific for 
      leukaemia or viral antigens through nilotinib was associated with a reduced 
      expansion of antigen peptide specific CD8+ T lymphocytes and with a decreased 
      release of interferon-gamma and granzyme B by these cells as analysed by flow 
      cytometry and enzyme-linked immunospot (ELISPOT) assays. The inhibitory effect 
      caused by nilotinib was two times stronger than by imatinib. These effects were 
      mediated through the inhibition of the phosphorylation of ZAP-70, Lck and ERK 1/2 
      and the NF-kappaB signalling transduction pathway. Taken together, we observed a 
      strong suppressive impact of nilotinib on the CD8+ T lymphocyte function which 
      should be considered carefully in the framework of allogeneic stem cell 
      transplantation or other T cell based immunotherapies.
FAU - Chen, J
AU  - Chen J
AD  - Third Department of Internal Medicine, University of Ulm, Ulm, Germany.
FAU - Schmitt, A
AU  - Schmitt A
FAU - Chen, B
AU  - Chen B
FAU - Rojewski, M
AU  - Rojewski M
FAU - Rubeler, V
AU  - Rubeler V
FAU - Fei, F
AU  - Fei F
FAU - Yu, Y
AU  - Yu Y
FAU - Yu, X
AU  - Yu X
FAU - Ringhoffer, M
AU  - Ringhoffer M
FAU - von Harsdorf, S
AU  - von Harsdorf S
FAU - Greiner, J
AU  - Greiner J
FAU - Gotzz, M
AU  - Gotzz M
FAU - Guillaume, P
AU  - Guillaume P
FAU - Dohner, H
AU  - Dohner H
FAU - Bunjes, D
AU  - Bunjes D
FAU - Schmitt, M
AU  - Schmitt M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080111
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - F41401512X (nilotinib)
SB  - IM
CIN - J Cell Mol Med. 2009 Mar;13(3):599-601. PMID: 19374687
MH  - Antineoplastic Agents/*pharmacology
MH  - CD8-Positive T-Lymphocytes/*drug effects/immunology
MH  - Case-Control Studies
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
MH  - Pyrimidines/*pharmacology
MH  - Receptors, Antigen, T-Cell/*drug effects/immunology
MH  - Signal Transduction/*drug effects
PMC - PMC4506175
EDAT- 2008/01/16 09:00
MHDA- 2009/03/04 09:00
PMCR- 2008/10/01
CRDT- 2008/01/16 09:00
PHST- 2008/01/16 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
PHST- 2008/01/16 09:00 [entrez]
PHST- 2008/10/01 00:00 [pmc-release]
AID - JCMM234 [pii]
AID - 10.1111/j.1582-4934.2008.00234.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2008 Oct;12(5B):2107-18. doi: 10.1111/j.1582-4934.2008.00234.x. 
      Epub 2008 Jan 11.