Differential Bone Marrow Homing Capacity of VLA-4 and CD38 High Expressing Chronic Lymphocytic Leukemia Cells 英文参考文献.docVIP

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Differential Bone Marrow Homing Capacity of VLA-4 and CD38 High Expressing Chronic Lymphocytic Leukemia Cells 英文参考文献.doc

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Differential Bone Marrow Homing Capacity of VLA-4 and CD38 High Expressing Chronic Lymphocytic Leukemia Cells 英文参考文献

DifferentialBoneMarrowHomingCapacityofVLA-4and CD38HighExpressingChronicLymphocyticLeukemia Cells GabrieleBrachtl1,KarineSahakyan1,UrsulaDenk1,TamaraGirbl1,BeateAlinger2,SebastianW. Hofbauer1,DanielNeureiter2,JosefinaPin?o′nHofbauer1,AlexanderEgle1,RichardGreil1,TanjaNicole Hartmann1* 1Laboratory for Immunological and Molecular Cancer Research, Third Medical Department with Hematology, Oncology, Hemostaseology, Infectiology and Rheumatology,PrivateMedicalUniversityHospital,Salzburg,Austria,2InstituteofPathology,ParacelsusMedicalUniversity,Salzburg,Austria Abstract Background:VLA-4andCD38predictapoorclinicaloutcomeinchroniclymphocyticleukemia(CLL).WeusedCLLsamples withdiscordantVLA-4/CD38risktoaddresstheirindividualrolesinhumanbonemarrowinfiltration(BM),CLLcellhoming tomurineBM,andinsupportiveCLLcell-stromalcellinteractions. Methods:VLA-4,CD38,andKi-67expressionwasmeasuredinCLLcellsfromperipheralblood(PB)andbonemarrow(BM) aspirates. CLL BM infiltration rates, routinely determined by Pathology, were correlated to VLA-4 and CD38 expression. Short-termhomingcapacityofCLLcellswasevaluatedbyadoptivetransferexperiments.CLLcellviabilityandadhesionin stromalcellco-culturewasdetermined. Results:About20%ofCLLsamplesinourcohortdisplayeddiscordantVLA-4andCD38risk,witheitherhighVLA-4andlow CD38 risk or vice versa. Using particularly such samples, we observed that VLA-4, and not CD38, was responsible for recirculationofCLLcellstomurineBM.HumanBMinfiltrationwasalsosignificantlyhigherinpatientswithhighVLA-4risk butnothighCD38risk.However,bothmoleculesactedasindependentprognosticmarkers.WhilebothVLA-4andCD38 expression were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations showed enriched Ki-67 expression,VLA-4didnotcontributetoCLLcellprotectionbystromalcellsinvitro. Conclusions:OurdataargueforaprominentroleofVLA-4butnotCD38expressioninthehomingofCLLcellstoBMniches andinhumanBMinfiltration,butonlyalimitedroleintheirprotectionbystromalcells. Citation:BrachtlG,S