Previous results indicated that miR-146b-5p is downregulated by TAL1, a 
transcription factor critical for early hematopoiesis that is frequently 
overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an 
oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in 
TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia 
T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, 
thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances 
the in vitro migration and invasion of T-ALL cells, associated with increased 
levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression 
in a TAL1-positive cell line extends mouse survival in a xenotransplant model of 
human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia 
acceleration and decreased mouse overall survival, paralleled by faster tumor 
infiltration of the central nervous system. Our results suggest that miR-146b-5p 
is a functionally relevant microRNA gene in the context of T-ALL, whose negative 
regulation by TAL1 and possibly other oncogenes contributes to disease 
progression by modulating leukemia cell motility and disease aggressiveness.