Ovid: Welcome to Ovid

E[mu]/miR-125b transgenic mice develop lethal B-cell malignancies.
Enomoto, Y 1; Kitaura, J 1; Hatakeyama, K 2; Watanuki, J 3; Akasaka, T 4; Kato, N 1; Shimanuki, M 3; Nishimura, K 1; Takahashi, M 1; Taniwaki, M 5; Haferlach, C 6; Siebert, R 7; Dyer, MJS 4; Asou, N 8; Aburatani, H 9; Nakakuma, H 3; Kitamura, T 1,10; Sonoki, T 3
[Article] Leukemia. 25(12):1849-1856, December 2011.

(Format: HTML, PDF)

: MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overex-pression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (E[mu]/miR-125b-TG mice). E[mu]/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the E[mu]/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a proapoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.