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MicroRNA miR-125b causes leukemia

Author(s)
Bousquet, Marina; Harris, Marian H.; Zhou, Beiyan; Lodish, Harvey F
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Abstract
MicroRNA miR-125b has been implicated in several kinds of leukemia. The chromosomal translocation t(2;11)(p21;q23) found in patients with myelodysplasia and acute myeloid leukemia leads to an overexpression of miR-125b of up to 90-fold normal. Moreover, miR-125b is also up-regulated in patients with B-cell acute lymphoblastic leukemia carrying the t(11;14)(q24;q32) translocation. To decipher the presumed oncogenic mechanism of miR-125b, we used transplantation experiments in mice. All mice transplanted with fetal liver cells ectopically expressing miR-125b showed an increase in white blood cell count, in particular in neutrophils and monocytes, associated with a macrocytic anemia. Among these mice, half died of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, or a myeloproliferative neoplasm, suggesting an important role for miR-125b in early hematopoiesis. Furthermore, coexpression of miR-125b and the BCR-ABL fusion gene in transplanted cells accelerated the development of leukemia in mice, compared with control mice expressing only BCR-ABL, suggesting that miR-125b confers a proliferative advantage to the leukemic cells. Thus, we show that overexpression of miR-125b is sufficient both to shorten the latency of BCR-ABL–induced leukemia and to independently induce leukemia in a mouse model.
Date issued
2010-12
URI
http://hdl.handle.net/1721.1/64991
Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Bousquet, M. et al. “MicroRNA miR-125b Causes Leukemia.” Proceedings of the National Academy of Sciences 107.50 (2010) : 21558-21563. ©2011 by the National Academy of Sciences.
Version: Final published version
ISSN
1091-6490

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