Prognostic Significance of miR-181a and miR-181b Expression and NPM1 Mutations in Patients With Acute Myeloid Leukemia Undergoing Hematopoietic Stem Cell Transplant.
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OBJECTIVES: MicroRNAs play an essential role in acute myeloid leukemia pathogenesis, including cell survival, differentiation, and proliferation. We aimed to examine miR -181a and miR -181b expression levels in patients with recently diagnosed acute myeloid leukemia, focusing on those who developed acute graft -versus -host disease, and to characterize NPM 1 mutations present in these patients. MATERIALS AND METHODS: We compared miR -181a and miR-181b expression levels in 150 newly diagnosed patients with acute myeloid leukemia and NPM1 mutation subtypes and healthy controls, along with various risk groups (high, intermediate, favorable risk ), M3 versus non -M 3, with and without graft -versus -host disease, and response or no response to therapy. We used quantitative SYBR green real -time polymerase chain reactions for evaluations. RESULTS: Patients with acute myeloid leukemia and NPM1 mutation B exhibited significantly higher miR -181a expression (3.4 -fold increase, P = .008 ), whereas miR -181b was reduced across all patients with acute myeloid leukemia (18.3 -fold decrease, P < .001 ). Receiver operating characteristic analysis demonstrated that miR -181a distinguished acute myeloid leukemia from controls (area under the curve of 0.81 ). Among recipients of hematopoietic stem cell transplant, those with versus those without acute graft -versus -host disease and NPM1 mutation C showed significantly elevated miR -181a expression (P = .002 ), with 80.0 % sensitivity and 85.7 % specificity for predicting acute graft -versus -host disease. Baseline miR -181a expression in patients with NPM1 mutation B was significantly associated with response to therapy (P = .001 ). Expression of miR-181a also differed between M3 and non-M3 French-American-British subtypes (P = .05 ). NPM1 mutation A was significantly more prevalent in patients with acute myeloid leukemia compared with controls (P = .04 ). CONCLUSIONS: miR -181a is a potential diagnostic and prognostic biomarker in acute myeloid leukemia, particularly for distinguishing French -American -British subtypes and predicting acute graft -versus -host disease in patients with NPM1 mutations undergoing hematopoietic stem cell transplant. These findings warrant further validation in larger cohorts.