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Firas Sadiyah

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https://www.readbyqxmd.com/read/23852341/bach2-mediates-negative-selection-and-p53-dependent-tumor-suppression-at-the-pre-b-cell-receptor-checkpoint
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Srividya Swaminathan, Chuanxin Huang, Huimin Geng, Zhengshan Chen, Richard Harvey, Huining Kang, Carina Ng, Björn Titz, Christian Hurtz, Mohammed Firas Sadiyah, Daniel Nowak, Gabriela B Thoennissen, Vikki Rand, Thomas G Graeber, H Phillip Koeffler, William L Carroll, Cheryl L Willman, Andrew G Hall, Kazuhiko Igarashi, Ari Melnick, Markus Müschen
The B cell-specific transcription factor BACH2 is required for affinity maturation of B cells. Here we show that Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin VH-DJH gene segments. After productive VH-DJH gene rearrangement, pre-B cell receptor signaling ends BACH2-mediated negative selection through B cell lymphoma 6 (BCL6)-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, the BACH2-mediated checkpoint control is compromised by deletions, rare somatic mutations and loss of its upstream activator, PAX5...
August 2013: Nature Medicine
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