The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development
Copyright policy )The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development
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.
- The University of Texas System United States
- National Institute of Allergy and Infectious Diseases United States
- The University of Texas at Austin United States
- UT SOUTHWESTERN MEDICAL CENTER
- Dalian Polytechnic University China (People's Republic of)
Adult, Male, Cell Survival, Amino Acid Motifs, Article, Cell Line, Tumor, Animals, Humans, Receptors, Immunologic, Cyclic AMP Response Element-Binding Protein, Aged, Cell Proliferation, Mice, Knockout, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Middle Aged, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Neoplastic Stem Cells, Female, RNA Interference
Adult, Male, Cell Survival, Amino Acid Motifs, Article, Cell Line, Tumor, Animals, Humans, Receptors, Immunologic, Cyclic AMP Response Element-Binding Protein, Aged, Cell Proliferation, Mice, Knockout, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Middle Aged, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Neoplastic Stem Cells, Female, RNA Interference
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).125 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!