期刊
NATURE CELL BIOLOGY
卷 17, 期 5, 页码 665-U286出版社
NATURE PORTFOLIO
DOI: 10.1038/ncb3158
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资金
- NIH [1R01CA172268]
- Leukemia & Lymphoma Society [1024-14, TRP-6024-14, CPRIT RP140402]
- March of Dimes Foundation [1-FY14-201]
- Robert A. Welch Foundation [I-1834]
- When Everyone Survives Foundation
- V Foundation for Cancer Research
- William Lawrence and Blanche Hughes Fund
- National Cancer Institute [4 R00CA151457-03]
- Leukemia Lymphoma Society
- Susan G. Komen Foundation [RO1GM087305]
- National Institute Allergy and Infectious Diseases
- NIH/NCI [R01 CA164346]
- Ladies Leukemia Leaque, Developmental Research Awards in Leukemia [SPORE CA100632]
- Center for Inflammation and Cancer
- IRG
- Center for Genetics and Genomics
- Sister Institution Network fund
- Physician Scientist Award of the Univmsity of Texas MD Anderson Care Center
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.
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