INCREASED  TYRO3  AND  PROTEIN  S  EXPRESSION  IN CIRCULATING  MONOCYTES  AND  T  CELLS  SEEM  TO CORRELATE  WITH  ACTIVITY  OF  LCH

ROSSO, DIEGO A.; TESSONE, LICINA; HELENA, GRACIELA; CARRERA SILVA, EUGENIO A.; ERRASTI, ANDREA E.

Atenas

Congreso; 31st Annual Meeting of the Histiocyte Society; 2015

Histiocyte Society

Background/Purpose:  The  TAM  receptor  tyrosine  kinases  (RTKs),TYRO3,  AXL,  and  MERTK,  together  with  their  cognate  agonistsGAS6  and  Protein  S  (PROS1)  play  an  essential  role  in  the  resolutionof  inflammation.  Additionally,  TAM  receptors  are  aberrantlyexpressed  in  multiple  haematological  and  epithelial  malignanciespromoting  survival,  chemoresistance  and  motility.  Our  aim  was  toexplore  the  role  of  the  TAM  system  in  the  immunologicaldysregulation  of  pediatric  LCH.  Methods:  We  analyzed  the  expression  of  TAM  receptors  and  theirligands  in  peripheral  blood  monocyte  and  T  lymphocyte  lineage(PBMC)  of  three  LCH  children  (LCH1-­3)  by  FACS  analysis.  Atsampling,  LCH1  was  an  8  month  old  (m.o.)  boy  untreated  with  abulky  mediastinum  mass  and  multiple  skin  lesions;;  LCH2  was  a  3year  old  girl  treated  during  the  first  year  of  life,  with  a  non-­activecutaneous  disease  and  LCH3  was  a  10  m.o.  girl  with  active  skindisease  and  under  non-­systemic  therapy.  PBMC  of  LCH1  wasanalyzed  again  after  6  weeks  of  vinblastine  and  meprednisonetreatment.Results:  Remarkable,  LCH1  who  presented  systemic  compromiseshowed  increased  circulating  CD11b  +  cells  (27%)  compared  withLCH2  (2%)  and  LCH3  (8%).  Furthermore,  PROS1  and  TYRO3  weremuch  more  expressed  in  the  monocytes  and  T  cells  compartment  ofLCH1  compared  with  LCH2  and  LCH3  patients.  Interestingly,  after  6weeks  of  treatment  LCH1  showed  a  reduction  of  circulating  CD11b+cells  (14%)  concomitant  with  lower  levels  of  PROS1  (14-­folddecrease)  and  TYRO3  (3-­fold  decrease)  expression  in  the  CD11b+population.  Conclusion:  Our  results  show  that  higher  levels  of  TYRO3  andPROS1  are  associated  with  LCH  activity  and  could  be  an  indicator  ofsystemic  compromise  in  pediatric  LCH.