Up regulation of TYRO3 tyrosine kinase receptor and PROS1 in the myeloid compartment of patients with Langerhans cell Histiocytosis (LCH)

OLEXEN CM; NOWAK W; CASTELLANOS COLLAZO O; ORTIZ WILCZYÑSKI JM; TESSONE L; ESTECHO IG; ROSSO DA; ERRASTI AE; CARRERA SILVA EA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC-SAI-SAFIS 2018; 2018

SAIC-SAI-SAFIS

TYRO3, AXL and MERTK (TAM) tyrosine kinase receptors and theiragonist Protein S (PROS1) have been identified as negative regulatorsof the immune response, as well as non-classical proto-oncogenesaberrantly expressed in multiple haematological and epithelialmalignancies. Langerhans Cell (LC) Histiocytosis (LCH) is a disordercharacterized by an abnormal accumulation of CD207+CD1a+myeloid cells in almost any tissue. The etiology of this disease is stillunder scientific discussion and it is not clear if LCH results from malignanttransformation or unbalanced immune response that leadsto the proliferation of pathogenic LC-like cells. Our aim is to explorethe role of the TAM axis in the pathogenesis of pediatric LCH. Weanalyzed the expression of TAM receptors and PROS1 in peripheralblood mononuclear cells of pediatric patients with confirmed diagnosisof LCH with active disease (AD) or non-active disease (NAD) andadult controls. The expression levels of PROS1 and TAM receptorswere determined by flow cytometry and expressed as fold increaseof mean fluorescence intensity (MFI) compared to the isotype control.Circulating total CD11b+ fraction was significantly expanded inAD (36.4 ± 3.7 %) vs NAD (18.9 ± 1.7 %) and adult controls (24.9 ±1.3 %). Interestingly, this fraction that is considered the main sourceof inflammatory myeloid cells, showed higher levels of PROS1 inAD (14.2-fold) compared with NAD (6-fold) and adult controls (6.7-fold). TYRO3 was also up regulated in circulating CD11b+ cells inAD (10.6-fold) compared with NAD (5-fold) and adult controls (4.5-fold). Our results show that higher levels of TYRO3 and PROS1are associated with active and multisystem LCH suggesting that thisaxis could be involved in the expansion of precursor and pathologicalLC-like cells.