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Since2003,5patientswithX-linkedseverecombinedimmunodeficiencydevelopedaleukemia-likesyndromenearly2.5-5yearsafterbeingtreatedwithretroviralgenetherapy.4outofthese5patientsareinremissionafterchemotherapyandingoodconditionwithdetectablegenemarkinginperipheralbloodcells.Initiationoftransformationwastracedbacktoinsertionalactivationoftheproto-oncogeneLMN2,atranscriptionalcofactor,whichinadditiontoitsroleinHSCdevelopment,promotesself-renewalofcommittedTcellswhenoverexpressedtherebyfacilitatingtheacquisitionofadditionalmutations.
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