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Nat Cell Biol. 2015 May;17(5):665-77. doi: 10.1038/ncb3158. Epub 2015 Apr 27.

The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development.

Author information

1
Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
2
1] Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] School of Life Science and Medicine, Dalian University of Technology, Panjin, Liaoning 124221, China.
3
Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
4
Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
5
Department of Physiology and Pharmacology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon 97239, USA.
6
Cell and Developmental Biology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon 97239, USA.
7
Receptor Cell Biology Section, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland 20852, USA.
8
Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
9
1] Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.

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.

PMID:
25915125
PMCID:
PMC4417000
DOI:
10.1038/ncb3158
[Indexed for MEDLINE]
Free PMC Article

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