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Science 316 (5826): 860-866

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of B Versus T Lymphoid Lineage Fate Decision by the Proto-Oncogene LRF

Takahiro Maeda,1* Taha Merghoub,1 Robin M. Hobbs,1 Lin Dong,1 Manami Maeda,1* Johannes Zakrzewski,2 Marcel R.M. van den Brink,2 Arthur Zelent,4 Hirokazu Shigematsu,5 Koichi Akashi,5 Julie Teruya-Feldstein,3 Giorgio Cattoretti,6{dagger} Pier Paolo Pandolfi1,3{ddagger}

Abstract: Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell–instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage.

1 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
2 Department of Medicine and Immunology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
3 Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
4 Leukemia Research Fund Center at the Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, London, UK.
5 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Smith Building 770A, 1 Jimmy Fund Way, Boston, MA 02115, USA
6 Institute for Cancer Genetics, Columbia University, New York, NY 10032 USA.

* Present address: Department of Hematopoietic Stem Cell and Leukemia Research, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.

{dagger} Present address: Department of Pathology, Università degli Studi Milano-Bicocca and Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20052 Monza (MI), Italy.

{ddagger} To whom correspondence should be addressed. E-mail: p-pandolfi{at}ski.mskcc.org


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