A molecular and functional analysis of large granular lymphocyte expansions in patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors.
A molecular and functional analysis of large granular lymphocyte expansions in patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors.
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DOI：
10.3109/10428194.2010.550074
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发表时间：
2011-04
影响因子：
2.6
通讯作者：
Pinilla-Ibarz JA
中科院分区：
文献类型：
--
作者：
Powers JJ;Dubovsky JA;Epling-Burnette PK;Moscinski L;Zhang L;Mustjoki S;Sotomayor EM;Pinilla-Ibarz JA
Tyrosine kinase inhibitor (TKI) therapy has become the standard treatment for chronic myelogenous leukemia (CML). Off-target kinase inhibition has been implicated in the appearance of unique adverse effects, such as colitis and pleural effusions. In addition, some patients present oligoclonal expansions of large granular lymphocytes (LGLs). We sought to further investigate this phenomenon in 64 patients treated with 5 different TKIs. Clonal expansions of cytotoxic T lymphocytes (CTLs) were identified in all TKI-treated patient groups, but only in dasatinib-treated patients were these expansions characterized as LGLs. Survival factors known to be important in LGL leukemia (IL-15 transpresentation, plasma PDGF BB levels, NF-κB, and T-bet activation) were found to be associated with TKI-induced LGL expansions. Interestingly, patients with LGL expansions had increased cytotoxicity against non-transformed endothelial cells, which may play a role in observed autoimmune-like side effects. Our results indicate that CML patients treated with TKIs can develop T cell expansions, which can in certain cases be related with some adverse effects.
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影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
20.3
作者：
Ottmann, Oliver;Dombret, Herve;Coutre, Steven
通讯作者：
Coutre, Steven
影响因子：
20.3
作者：
Olavarria, Eduardo;Siddique, Shamyla;Craddock, Charles F.
通讯作者：
Craddock, Charles F.
DOI：
10.1080/13684730210002319
发表时间：
2002-01-01
期刊：
CYTOKINES CELLULAR & MOLECULAR THERAPY
影响因子：
--
作者：
Aswald, JM;Lipton, JH;Messner, HA
通讯作者：
Messner, HA
影响因子：
2.6
作者：
Fraser, Cara K.;Blake, Stephen J.;Hayball, John D.
通讯作者：
Hayball, John D.