Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice

TY - JOUR

T1 - Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice

AU - Costinean, Stefan

AU - Sandhu, Sukhinder K

AU - Pedersen, Irene M

AU - Tili, Esmerina

AU - Trotta, Rossana

AU - Perrotti, Danilo

AU - Ciarlariello, David

AU - Neviani, Paolo

AU - Harb, Jason

AU - Kauffman, Lauren Rachel

AU - Shidham, Aaditya

AU - Croce, Carlo Maria

N1 - Keywords: Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Transformation, Neoplastic; Down-Regulation; Gene Expression Regulation, Leukemic; Interleukin-6; Lymphoma, B-Cell; Mice; Mice, Transgenic; MicroRNAs; Phosphoric Monoester Hydrolases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cells, B-Lymphoid; Signal Transduction

PY - 2009

Y1 - 2009

N2 - We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

AB - We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

U2 - 10.1182/blood-2009-05-220814

DO - 10.1182/blood-2009-05-220814

M3 - Journal article

C2 - 19520806

SN - 0006-4971

VL - 114

SP - 1374

EP - 1382

JO - Blood

JF - Blood

IS - 7

ER -