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

To the Editor: MicroRNAs (miRNAs) are small, non-coding RNA of 20–22 nucleotides in length which can silence specific target genes through direct mRNA degradation, translational repression, or both. miRNAs are involved in several cellular processes like cell cycle, apoptosis, drug resistance and differentiation. In 2011, Schotte et al. reported different miRNA signatures in pediatric acute lymphoblastic leukemia (ALL) with various genetic subtypes and drug-resistance. miR125b, miR-99a, and miR-100 were upregulated 20-fold in vincristine and daunorubicin-resistant ALL cells. Recent reports suggested that co-expression of miR-125b in combination with miR-100, or miR-99a, or miR-100 and miR99a induces significant vincristine (VCR) resistance in ETV6RUNX1-positive Reh leukemic cells. The authors noted that the miR-125b isoforms, (miR-125b-1 and miR-125b-2), were located downstream to miR-100 and miR-99a, respectively. Also, both miR-100 and miR-99a differed by a single nucleotide. Therefore, coexpression of miR-125b/miR-99a, miR-125b/miR-100 or miR-125b/ miR-99a/miR-100 is required for VCR resistance. A growing body of evidence suggests the crucial role of miRNAs in the regulation of differentiation in normal as well as malignant hematopoiesis. Screening of miRNA for this drug