Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells

// Vadim V. Sumbayev 1 , Isabel Gonçalves Silva 1 , Jennifer Blackburn 1 , Bernhard F. Gibbs 1 , Inna M. Yasinska 1 , Michelle D. Garrett 2 , Alexander G. Tonevitsky 3 , Yuri A. Ushkaryov 1 1 School of Pharmacy, University of Kent, Chatham, Kent, ME4 4TB, United Kingdom 2 School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom 3 Hertsen Moscow Oncology Research Institute, Branch of The National Medical Research Radiological Center, Ministry of Health of The Russian Federation, 125284, Moscow, Russian Federation Correspondence to: Vadim V. Sumbayev, email: V.Sumbayev@kent.ac.uk Yuri A. Ushkaryov, email: Y.Ushkaryov@kent.ac.uk Keywords: latrophilin, myeloid leukaemia, mammalian target of rapamycin Received: March 17, 2016 Accepted: May 29, 2016 Published: June 14, 2016 ABSTRACT Acute myeloid leukaemia (AML) is a blood cancer affecting cells of myeloid lineage. It is characterised by rapid growth of malignant leukocytes that accumulate in the bone marrow and suppress normal haematopoiesis. This systemic disease remains a serious medical burden worldwide. Characterisation of protein antigens specifically expressed by malignant cells, but not by healthy leukocytes, is vital for the diagnostics and targeted treatment of AML. Here we report, for the first time, that the neuronal receptor latrophilin-1 is expressed in human monocytic leukaemia cell lines and in primary human AML cells. However, it is absent in healthy leukocytes. Latrophilin-1 is functional in leukaemia cells tested, and its biosynthesis is controlled through the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways. Our findings demonstrate that latrophilin-1 could be considered as a novel biomarker of human AML, which offers potential new avenues for AML diagnosis and treatment.