Expression of LYN and PTEN genes in chronic myeloid leukemia and their importance in therapeutic strategy.

摘要: Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib and dasatinib, are the current treatment of chronic myeloid leukemia (CML). BCR-ABL1 point mutations principal cause resistance to treatment; however other mechanisms could be involved in failure TKI therapy. LYN is a src protein that regulates survival responsiveness tumor cells by independent mechanism. PTEN suppressor gene downregulated CML stem its deletion associated with acceleration disease. In this study we evaluated expression LYN, ratio both genes 40 healthy donors (HD) 139 patients; 88 them resistant different phases disease 51 phase classified as optimal responders (OR) [40 treated imatinib or (OR-IN) 11 dasatinib (OR-D) therapy]. When analyzed values an increase was observed only advanced stages disease, however, when between genes, group patients (CP-IN) also showed significant increase. Resistant inhibitor, presented similar HD. addition, LYN/PTEN direct correlation transcript levels unmutated non-src inhibitors. We were able identify 8/35 (23%) cases CP-IN 4/12 (33%) accelerated blast (AP/BC-IN), which LYN/PTEN. Our data suggest may sensitive monitor progression under treatment. This detect related altered expression, suggesting change inhibitor would most suitable overcome resistance.