期刊
LEUKEMIA & LYMPHOMA
卷 52, 期 4, 页码 668-679出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2010.550074
关键词
Chronic myelogenous leukemia; tyrosine kinase inhibitors; large granular lymphocytes
资金
- Cancer Foundation Finland sr [100118, 110101] Funding Source: researchfish
- NCI NIH HHS [R01 CA129952, R01 CA112112, P30 CA076292] Funding Source: Medline
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 five 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 (interleukin-15 [[IL-15]] transpresentation, plasma platelet-derived growth factor [[PDGF]]-BB levels, nuclear factor-kappa kappa B [[NF-kappa kappa B]] 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 patients with CML treated with TKIs can develop T cell expansions, which can in certain cases be related to some adverse effects.
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