@article{783daff5d5ad4c13af44b5a3d08281dc,
title = "Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia",
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. Invivo treatment studies suggested that pre-BCR tyrosine kinase inhibitors are useful for the treatment of patients with pre-BCR+ ALL.",
author = "Huimin Geng and Christian Hurtz and Lenz, {Kyle B.} and Zhengshan Chen and Dirk Baumjohann and Sarah Thompson and Goloviznina, {Natalya A.} and Chen, {Wei Yi} and Jianya Huan and Dorian LaTocha and Erica Ballabio and Gang Xiao and Lee, {Jae Woong} and Anne Deucher and Zhongxia Qi and Eugene Park and Chuanxin Huang and Rahul Nahar and Kweon, {Soo Mi} and Seyedmehdi Shojaee and Chan, {Lai N.} and Jingwei Yu and Kornblau, {Steven M.} and Bijl, {Janetta J.} and Ye, {B. Hilda} and {Mark Ansel}, K. and Elisabeth Paietta and Ari Melnick and Hunger, {Stephen P.} and Peter Kurre and Tyner, {Jeffrey W.} and Loh, {Mignon L.} and Roeder, {Robert G.} and Druker, {Brian J.} and Burger, {Jan A.} and Milne, {Thomas A.} and Chang, {Bill H.} and Markus M{\"u}schen",
note = "Funding Information: We thank Michael L. Cleary (Stanford) for critical discussions, Arthur L. Shaffer and Louis M Staudt for inducible BCL6 constructs, Mark Kamps and David B. Sykes for inducible TCF3-PBX1 vectors, Lothar Hennighausen for Stat5ab fl/fl mice, and Julia Gastier-Foster and I-Ming Chen for fresh samples from the COG ALL Biology Bank (proposal number 2008-08). This work is supported by grants from the NIH/NCI through R01CA137060, R01CA139032, R01CA157644, R01CA169458, R01CA172558 (to M.M.), CA178765 and CA163068 (to R.G.R.), R00CA151457 and R01CA183947 (to J.W.T.), U10 CA98543 (COG Chair{\textquoteright}s grant), U10 CA98413 (COG Statistical Center), and U24 CA114766 (COG Specimen Banking), the Hyundai Hope on Wheels, the St. Baldrick{\textquoteright}s Foundation, the Leukemia & Lymphoma Society Specialized Center of Research (LLS SCOR) and Tucker{\textquoteright}s Toy Box Foundation (to B.H.C.), the William Lawrence and Blanche Hughes Foundation, the California Institute for Regenerative Medicine (CIRM; TR2-01816), Leukaemia and Lymphoma Research (to M.M.), the Medical Research Council and the National Institute for Health Research Oxford Biomedical Research Centre Program (to T.M. and E.B.). B.J.D. is supported by the Howard Hughes Medical Institute. M.M. is a Scholar of the Leukemia and Lymphoma Society and a Senior Investigator of the Wellcome Trust. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = mar,
day = "9",
doi = "10.1016/j.ccell.2015.02.003",
language = "English (US)",
volume = "27",
pages = "409--425",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}