Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation

Lck is a key target of imatinib and dasatinib in T-cell activation

“…However, it is also less specific and its range of targets includes the family of Src kinases, whose members have important roles in the growth and differentiation of various cell types. Both imatinib and dasatinib have been shown to suppress T-cell functions, [1][2][3][4][5] although the reasons for this are not fully established. The intracellular tyrosine kinase Lck is essential for the development and activation of T-cells and previous studies have shown that purified recombinant Lck can be inhibited by dasatinib and imatinib.…”

“…Indeed, in these studies, the median age at diagnosis was younger (50-57-years old) than usually noted for ET patients in population-based studies (67-73-years old). 4,5 Moreover, long-term outcomes in ET patients from population-based studies, usually involving o100 patients, are rarely investigated. Finally, in these studies, survival was generally based on observed mortality, a good but incomplete representation of overall mortality: given the old age (465 years) of half of the patients at the time of diagnosis, more specific analyses such as relative mortality, that describes mortality directly associated with the disease, thus ruling out biases related to age or other illnesses, should be carried out.…”

“…Nevertheless, this high rate of mortality allowed us to better analyze survival on a sufficiently large number of events (n ¼ 125) compared with previous studies with a low number of deaths (ranging from 20 to 30). 1,4 When relative survival was analyzed, that is focusing on deaths directly associated with the disease, mortality because of ET was low in the first 10 years of evolution, as survival was 83% at 10 years. However, it decreased to 47% after 20 years of follow-up, with a generally regular curve with no steep falls.…”

Development of severe sclerotic chronic GVHD during treatment with dasatinib

“…3,4,[7][8][9] Dasatinib's ability to target T-cell signaling and enhance the inhibitory effect of cyclosporine suggests an additional rationale for its use in cGVHD treatment. 10 We describe the case of a 22-year-old Latin American man who developed de novo severe sclerotic cGVHD after 10/10 HLA matched unrelated donor peripheral blood hematopoietic SCT (HSCT), in spite of continuous treatment with dasatinib after HSCT for the presence of CML. He was diagnosed with Ph þ CML in 2005, which was resistant to standard and high-dose imatinib.…”

Efficacy of dasatinib in a chronic myeloid leukemia patient with disease molecular relapse and chronic GVHD after haploidentical BMT: an immunomodulatory effect?

“…Schade et al 3 recently proved that dasatinib inhibits in vitro TCR signaling and expression of activation markers, cytokine production and proliferation. These authors showed that dasatinib is able to inhibit inflammation, leukocyte recruitment and host or allograft tissue destruction in vitro.…”