Does the presence of anti-HIV miRNAs in monocytes explain their resistance to HIV-1 infection?

The patient succumbed to CNS disease 3 months afterward, despite CNS-directed chemotherapy. Sequencing of the BCR-ABL kinase domain from BM blasts, at the time of BC, and CSF tumor cells, at CNS relapse, did not show any mutation. The lack of BM blastosis, the reduced marrow BCR-ABL levels and the absence of a mutated clone, in BM and CSF, at the onset of meningeal leukemia, indicate that systemic dasatinib failed to prevent CSF disease while still controlling extra-CNS leukemia. Thus, relapse was most probably due to suboptimal penetrance/activity of the drug in CNS given the low dasatinib dose (100 mg per day) used being the patient in CP. In the 4 months preceding CNS progression, the patient was not given comedications known to decrease the plasma concentrations of dasatinib,4,5 including CYP4503A4 inducers, but rather received the CYP4503A4 inhibitor itraconazole. Therefore, even though we did not assess plasma levels, it is reasonable to exclude a negative influence of comedications on dasatinib bioavailability. Dasatinib achieves CSF concentrations of 5.0% to 28% of those found in the plasma and Authors speculated that the biologic potency of dasatinib and/or the lack of protein binding may explain antitumor activity at low CSF levels.1 However, approximately 50% of patients received steroids and/or other intrathecal agents before, together with, or soon after dasatinib, suggesting that this agent alone is unable exert a proper control of CNS disease in all cases.1,6 Factors other than tumor cell resistance might influence dasatinib activity in the CNS, including suboptimal systemic dosing. Further pharmacokinetic studies are needed to identify patients in whom dasatinib alone may effectively control CNS disease. Ferdinando Frigeri, Manuela Arcamone, Luigia Luciano, Raffaele Di Francia, Fabrizio Pane, and Antonio Pinto