ContentslistsavailableatScienceDirectBloodReviewsjournalhomepage:www.elsevier.com/locate/blreReviewAstormintheniche:Iron,oxidativestressandhaemopoiesisFedericaPiloa,EmanueleAngeluccib,⁎aHematologyandTransplantCenter,OspedaleOncologicodiRiferimentoRegionale"ArmandoBusinco",AziendaOspedalieraBrotzu,Cagliari,Italy.bHematologyandTransplantCenter,OspedalePoliclinicoSanMartino,Genova,ItalyARTICLEINFOKeywords:IronOxidativestressHaematopoieticstemcellsClonalevolutionABSTRACTIron,althoughessential,isharmfulinhighamounts.Oxidativestressasaresultofexcessreactiveoxygenspecies(ROS)andaprooxidative/antioxidativeimbalancebetweenROSproductionandelimination,playakeyroleincellulardamage.ThereisevidencetosupporttheroleofROSinthepathogenesisofarangeofdiseasesincludingthemyelodysplasticsyndromes(MDS)andleukaemia.Oxidativestressseemstoaffecttheself-renewal,pro-liferationanddifferentiationofhaematopoieticstemcellsandimpaircellgrowth.Threeaspectsofthesede-fectivehaemopoieticmechanismsmaybeassociatedwiththeactivitiesofROS:clonalevolution,haematologicalimprovementandrecoveryofhaemopoiesisafterhaematopoieticstemcelltransplantation(HSCT).Thisreviewaimstoprovidehaematologistswithanoverviewofresultsfrominvitroandmurinemodelsandpreliminaryclinicalevidenceonthediagnostic,prognosticandtherapeuticimplicationsofthecomplexinteractionsbetweenthehaemopoieticniche,iron,oxidativestressandinadequatehaemopoiesis.1.IntroductionIronisfundamentalformanycellularfunctionssuchasthecellcycleofgrowthandreplication,metabolismandDNAsynthesis/repairandiron-requiringproteinssuchasFe-sulphurclusterproteinsthatareabundantinmitochondria[1].However,theabilitytogainandloseelectronsgivesironthepossibilityofparticipatinginpotentiallyharmfulfreeradical-generatingreactions,producingthehydroxylra-dical(OH)–areactiveoxygenspecies(ROS)basedontheFentonre-action[2].Thehydroxylradical,themostreactivechemicalspeciesinbiologicalsystems,whenpresentinexcess,cannotonlydamagelipids,proteins,andmitochondriabutalsocauseoxidativeDNAdamag...
