An increased expression of PI‐PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: phospholipase C β;    1;    methylation;    gene expression;    hematological malignancies;    epigenetic therapy;   

DOI  :  10.1189/jlb.2MA1114-541R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThisstudytestedthehypothesisthatPI‐PLCβ1isassociatedwithmyeloiddifferentiationandthatitsexpressioncouldbeusefulforpredictingtheresponseofMDSpatientstoazacitidine,astheclinicaleffectofepigenetictreatmentsisoftendetectableonlyafterseveralcyclesoftherapy.Tothisend,PI‐PLCβ1wasquantifiedon70MDSpatients(IPSSrisk:13Low,20Int‐1,31Int‐2,6High)atbaselineandduringthefirst3cyclesofazacitidine.Resultswerethencomparedwiththehematologicresponse,asassessedafterthesixthcycleofazacitidinetherapy.Overall,60patientscompleted6cyclesofazacitidine,andforthem,aclinicalandmolecularevaluationwaspossible:37ofthesepatients(62%)showedaspecificincreaseofPI‐PLCβ1mRNAwithinthefirst3cycles,whichwasassociatedwithalongerdurationofresponseandwithanincreasedmyeloiddifferentiation,asevidencedbyPI‐PLCγ2inductionandtherecruitmentofspecificmyeloid‐associatedtranscriptionfactorstothePI‐PLCβ1promoterduringazacitidineresponse.Moreover,theincreaseofcyclinD3geneexpressionthroughoutallofthetherapyshowedthatPI‐PLCβ1‐dependentsignalingisindeedactivatedinazacitidineresponderpatients.Takentogether,ourresultsshowthatPI‐PLCβ1quantificationinMDSpredictstheresponsetoazacitidineandisassociatedwithanincreasedmyeloiddifferentiation...

【 授权许可】

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