MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBPα (C/EBPα-Cm)-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...

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Bibliographic Details
Published in:International journal of hematology 2012-09, Vol.96 (3), p.334-341
Main Authors: Enomoto, Yutaka, Kitaura, Jiro, Shimanuki, Masaya, Kato, Naoko, Nishimura, Koutarou, Takahashi, Mariko, Nakakuma, Hideki, Kitamura, Toshio, Sonoki, Takashi
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone Marrow Cells - pathology
Bone Marrow Transplantation
CCAAT-Enhancer-Binding Protein-alpha - genetics
Disease Progression
Gene Expression
Hematologic and hematopoietic diseases
Hematology
Leukemia, Myeloid - genetics
Leukemia, Myeloid - mortality
Leukemia, Myeloid - pathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Medicine
Medicine & Public Health
Mice
MicroRNAs - genetics
Mutation
Myeloid Cells - pathology
Oncology
Original Article
Transduction, Genetic
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Summary: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.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-012-1143-5