The resistance of leukemic stem cells to conventional therapies poses challenges to the long-term cure of various hematopoietic malignancies. In Nature Cell Biology, Kang et al. identify the surface receptor LAIR1 (which contains immunoreceptor tyrosine-based inhibitory motifs) as a potential therapeutic target expressed on leukemic stem cells. Many acute leukemia cell lines express LAIR1, but knockdown of LAIR1 via short hairpin RNA diminishes the viability of such cells in vitro and upon serial transplantation into mice; however, loss of LAIR1 expression does alter normal hematopoiesis. Collagen-mediated crosslinking of LAIR1 promotes its interaction with the phosphatase SHP-1, which acts as a scaffold to recruit the kinase CAMK1. This signaling axis activates the transcription factor CREB that enhances survival of leukemic stem cells. Interfering with this axis increases apoptosis of leukemic stem cells, which makes LAIR1 a potential target for therapeutic intervention.

Nat. Cell Biol. (27 April 2015) doi:10.1038/ncb3158