Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Interleukin‐3‐mediated regulation of β‐catenin in myeloid transformation and acute myeloid leukemia | |
关键词: Hox; gene‐; expression profiling; leukemic stem cell; | |
DOI : 10.1189/jlb.2AB1013-559R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Aberrantactivationofβ‐cateninisacommoneventinAMLandisanindependentpredictorofpoorprognosis.Althoughincreasedβ‐cateninsignalinginAMLhasbeenassociatedwithoncogenictranslocationproductsandactivatingmutationsintheFLT3R,themechanismsthatactivateβ‐catenininAMLmorebroadlyarestillunclear.Here,wedescribeanovellinkbetweenIL‐3signalingandtheregulationofβ‐catenininmyeloidtransformationandAML.InamurinemodelofHoxB8andIL‐3cooperation,weshowthatβ‐cateninproteinlevelsaremodulatedbyIL‐3andthatCre‐induceddeletionofβ‐cateninabolishesIL‐3‐dependentgrowthandcolonyformation.InIL‐3‐dependentleukemicTF‐1.8cells,weobservedincreasedβ‐cateninproteinlevelsandnuclearlocalizationinresponsetoIL‐3,andthiscorrelatedwithtranscriptionalinductionofβ‐catenintargetgenes.Furthermore,IL‐3promotedβ‐cateninaccumulationinasubsetofAMLpatientsamples,andgene‐expressionprofilingofthesecellsrevealedinductionofWNT/β‐cateninandTCF4genesignaturesinanIL‐3‐dependentmanner.Thisstudyisthefirsttolinkβ‐cateninactivationtoIL‐3andsuggeststhattargetingIL‐3signalingmaybeaneffectiveapproachfortheinhibitionofβ‐cateninactivityinsomepatientswithAML...
【 授权许可】
CC BY
【 预 览 】
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