MiR-125b and miR-99a encoded on chromosome 21 co-regulate vincristine resistance in childhood acute megakaryoblastic leukemia.

Vincristine (VCR) resistance remains a major challenge for the successful treatment of leukemias. MicroRNAs (miRNAs) have a role in proliferation, differentiation and apoptosis, and are associated with poor prognosis phenotypes. Co-expression of miR-125b and miR-99a contribute to VCR resistance to CMK cells due to actively transcribed miR99a/miR-125b locus on chromosome 21q21.1. Here, we show that miR-99a downregulates the targets FKBP51 and IGF1R in CMK cell lines which, in turn, increase p-Akt (Ser473) levels. Our results suggest that these miRNAs can possibly be used in the development of therapies for the treatment of leukemia.

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