Abstract
SummaryConventional strategies are not particularly successful in treatment of leukemia, and identification of signaling pathways crucial to the activity of leukemia 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 leukemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal hematopoiesis but abolishes leukemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signaling 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 signaling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.
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