MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia 英文参考文献.docVIP

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MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia 英文参考文献.doc

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MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia 英文参考文献

o PL SMEDICINE MPLW515LIsaNovelSomaticActivating MutationinMyelofibrosiswithMyeloid Metaplasia Yana Pikman1,Benjamin H.Lee1,Thomas Mercher1,Elizabeth McDowell1,Benjamin L.Ebert2,3,Maricel Gozo1, Adam Cuker1,Gerlinde Wernig1,Sandra Moore1,Ilene Galinsky2,Daniel J.DeAngelo2,Jennifer J.Clark2, Stephanie J.Lee2,Todd R.Golub2,3,4,Martha Wadleigh2,D.Gary Gilliland1,2,4,Ross L.Levine1,2* 1BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,2Dana-FarberCancerInstitute,HarvardMedicalSchool,Boston, Massachusetts,UnitedStatesofAmerica,3BroadInstituteofHarvardandMIT,Cambridge,Massachusetts,UnitedStatesofAmerica,4HowardHughesMedicalInstitute, Boston,Massachusetts,UnitedStatesofAmerica Funding:Supportedinpartby NationalInstitutesofHealthgrants DK50654andCA66996toDGGand bytheLeukemiaandLymphoma Society.Thefundershadnorolein studydesign,datacollectionand analysis,decisiontopublish,or preparationofthemanuscript. ABSTRACT Background The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF). Subsequent analysishasshownthatconstitutiveactivationoftheJAK-STATsignaltransductionpathwayis animportantpathogeneticeventinthesepatients,andthatenzymaticinhibitionofJAK2V617F maybeoftherapeuticbenefitinthiscontext.However,asignificantproportionofpatientswith ETorMFareJAK2V617F-negative.WehypothesizedthatactivationoftheJAK-STATpathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokinereceptors,includingtheerythropoietinreceptor(EPOR),thethrombopoietinreceptor (MPL),orthegranulocyte-colonystimulatingfactorreceptor(GCSFR). CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. AcademicEditor:CharlesSawyers, UniversityofCaliforniaLosAngeles, UnitedStatesofAmerica Citation:PikmanY,LeeBH,Mercher T,McDowellE,EbertBL,etal.(2006) MPLW515Lisanovelsomatic activatingmutationinmyelofib