Details

Autor(en) / Beteiligte

• Enomoto, Yutaka
• Kitaura, Jiro
• Shimanuki, Masaya
• Kato, Naoko
• Nishimura, Koutarou
• Takahashi, Mariko
• Nakakuma, Hideki
• Kitamura, Toshio
• Sonoki, Takashi

Titel

MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBP[alpha] (C/EBP[alpha]-C^sup m^)-induced myeloid leukemia

Ist Teil von

• International journal of hematology, 2012-09, Vol.96 (3), p.334

Ort / Verlag

Tokyo: Springer Nature B.V

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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^sup +^/CD11b^sup +^ or GFP^sup +^/Gr^sup -^1^sup +^ 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^sup 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.[PUBLICATION ABSTRACT]