MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBPα (C/EBPα-C(m))-induced myeloid leukemia.

MicroRNA-125b-1 (miR-125b-1) is a target of the chromosomal translocations t(11;14)(q24;q32) and t(2;11)(p21;q23), which are found in human B-lymphoid and myeloid malignancies, respectively. These translocations result in overexpression of mature miR-125b, consisting of 22 nucleotides. To analyze the role of miR-125b-1 in leukemogenesis, we created a bone marrow transplantation model using a retrovirus vector containing GFP expression elements. Sole transduction of miR-125b-1 into bone marrow cells resulted in expansion of hematopoietic cells expressing GFP. Compared with cells lacking GFP expression, we observed that GFP(+)/CD11b(+) or GFP(+)/Gr(-)1(+) cells were increased in the bone marrow and spleen. Although previous studies reported sole induction of miR-125b-induced leukemia, we did not find leukemic transformation in our model. Transduction of miR-125b-1 did accelerate myeloid tumors induced by a C-terminal mutant of CAAT-enhancer binding protein (C/EBPα-C(m)), a class II-like mutation. As miR-125b has been shown to hasten the development of leukemia in a BCR/ABL-transduced animal model, our present results support the conclusion that overexpression of miR-125b cooperates with other genetic alterations in the pathogenesis of myeloid malignancies.