MicroRNAs in normal and malignant hematopoiesis. The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children. Nat Genet 2007 39: 593–595.Ĭlappier E, Cuccuini W, Kalota A, Crinquette A, Cayuela J-M, Dik WA et al. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Lahortiga I, De Keersmaecker K, Van Vlierberghe P, Graux C, Cauwelier B, Lambert F et al. Alu elements mediate MYB gene tandem duplication in human T-ALL. O′Neil J, Tchinda J, Gutierrez A, Moreau L, Maser RS, Wong KK et al. Critical roles for c-Myb in hematopoietic progenitor cells. Transcription factors in myeloid development: balancing differentiation with transformation. Transcriptional regulation of granulocyte and monocyte development. Transcriptional regulation of erythropoiesis: an affair involving multiple partners. Hematopoietic cytokines, transcription factors and lineage commitment. These results support the notion that miRNAs not only function to provide precision to developmental programs but also are essential determinants in the control of variable potential functions of a single gene during hematopoiesis. Both miRNAs are required but not sufficient individually to precisely regulate the cell fate decision between erythroid and megakaryocytic lineages during definitive hematopoiesis in vivo. We further provide evidence that specification of thrombocyte versus erythrocyte cell lineages is altered by the concerted activities of the microRNAs (miRNAs) miR-126 and miR-150. We show that knockdown of miR-126 results in increased c-Myb levels and promotes erythropoiesis at the expense of thrombopoiesis in vivo. In this study, we show that miR-126 is a novel physiological regulator of the proto-oncogene c-myb during definitive hematopoiesis. Precise regulatory mechanisms are required to appropriately modulate the cellular levels of transcription factors controlling cell fate decisions during blood cell development.
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