@article{e5bdca46ff0c4ec78af4d7e092788c95,
title = "The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development",
abstract = "Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.",
author = "Xunlei Kang and Zhigang Lu and Changhao Cui and {Deng Ph.D.}, Mi and Yuqi Fan and Baijun Dong and Xin Han and Fuchun Xie and Tyner, {Jeffrey W.} and Coligan, {John E.} and Collins, {Robert H} and Xiangshu Xiao and You, {M. James} and Chengcheng Zhang",
note = "Funding Information: We would like to thank H. Saya from Keio University School of Medicine for the pMX-IG N-Myc vector. We appreciate the support of staff of the tissue bank at the Department of Hematopathology, the University of Texas MD Anderson Cancer Center. Support to C.C.Z. was from NIH grant 1R01CA172268, Leukemia & Lymphoma Society Awards 1024-14 and TRP-6024-14, CPRIT RP140402, March of Dimes Foundation grant 1-FY14-201, Robert A. Welch Foundation grant I-1834, and When Everyone Survives Foundation. J.W.T. is supported by grants from the V Foundation for Cancer Research, the William Lawrence and Blanche Hughes Fund, and the National Cancer Institute (4 R00CA151457-03), and the Leukemia & Lymphoma Society. X.X. is supported by Susan G. Komen Foundation and RO1GM087305. J.E.C. is supported by the intramural program of the National Institute of Allergy and Infectious Diseases. M.J.Y. is supported in part by NIH/NCI R01 CA164346, Ladies Leukemia League, Developmental Research Awards in Leukemia SPORE CA100632, and Center for Inflammation and Cancer, IRG, Center for Genetics and Genomics, Sister Institution Network Fund and Physician Scientist Award of the University of Texas MD Anderson Cancer Center.",
year = "2015",
month = may,
day = "5",
doi = "10.1038/ncb3158",
language = "English (US)",
volume = "17",
pages = "665--677",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "5",
}