Members of the miR-99/100˜125 tricistrons cooperatively induce a pre-leukemic phenotype

Introduction: Acute promyelocytic leukemia (APL) is characterized by the accumulation of immature myeloid progenitors. The microRNAs (miRNAs) miR-100 and miR-125b, members of the conserved miR-99/100˜125b tricistrons, are found to be upregulated in APL, although their role in leukemia and myeloid differentiation is yet to be deciphered. Results: Using a lentiviral Red-Green-Blue (RGB) marking system to investigate genetic interaction as well as eight different miRNA mono-, bi- or tricistronic constructs, we showed that overexpression of miR-125b with miR-99 and/or let-7c leads to an inhibition of myeloid differe…