| Literature DB >> 25759025 |
Huimin Geng1, Christian Hurtz1, Kyle B Lenz2, Zhengshan Chen1, Dirk Baumjohann3, Sarah Thompson2, Natalya A Goloviznina4, Wei-Yi Chen5, Jianya Huan4, Dorian LaTocha6, Erica Ballabio7, Gang Xiao1, Jae-Woong Lee1, Anne Deucher1, Zhongxia Qi1, Eugene Park1, Chuanxin Huang8, Rahul Nahar1, Soo-Mi Kweon1, Seyedmehdi Shojaee1, Lai N Chan1, Jingwei Yu1, Steven M Kornblau9, Janetta J Bijl10, B Hilda Ye11, K Mark Ansel3, Elisabeth Paietta12, Ari Melnick8, Stephen P Hunger13, Peter Kurre4, Jeffrey W Tyner14, Mignon L Loh15, Robert G Roeder16, Brian J Druker17, Jan A Burger9, Thomas A Milne7, Bill H Chang2, Markus Müschen18.
Abstract
Studying 830 pre-B ALL cases from four clinical trials, we found that human ALL can be divided into two fundamentally distinct subtypes based on pre-BCR function. While absent in the majority of ALL cases, tonic pre-BCR signaling was found in 112 cases (13.5%). In these cases, tonic pre-BCR signaling induced activation of BCL6, which in turn increased pre-BCR signaling output at the transcriptional level. Interestingly, inhibition of pre-BCR-related tyrosine kinases reduced constitutive BCL6 expression and selectively killed patient-derived pre-BCR(+) ALL cells. These findings identify a genetically and phenotypically distinct subset of human ALL that critically depends on tonic pre-BCR signaling. In vivo treatment studies suggested that pre-BCR tyrosine kinase inhibitors are useful for the treatment of patients with pre-BCR(+) ALL.Entities:
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Year: 2015 PMID： 25759025 PMCID： PMC4618684 DOI： 10.1016/j.ccell.2015.02.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743