title: MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBPα (C/EBPα-C(m))-induced myeloid leukemia.
abstract: 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.
authors: Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors: Yutaka
authors: Y
authors: Enomoto
authors: Jiro
authors: J
authors: Kitaura
authors: Masaya
authors: M
authors: Shimanuki
authors: Naoko
authors: N
authors: Kato
authors: Koutarou
authors: K
authors: Nishimura
authors: Mariko
authors: M
authors: Takahashi
authors: Hideki
authors: H
authors: Nakakuma
authors: Toshio
authors: T
authors: Kitamura
authors: Takashi
authors: T
authors: Sonoki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D018450:Disease Progression; D015870:Gene Expression; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D022423:Myeloid Cells / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse