Galectin‐12 inhibits granulocytic differentiation of human NB4 promyelocytic leukemia cells while promoting lipogenesis

[摘要] Asamemberofthegalectinfamilyofanimallectins,galectin‐12ispreferentiallyexpressedinadipocytesandleukocytes.Inadipocytes,galectin‐12isassociatedwithlipiddropletsandregulateslipidmetabolismandenergybalance,whereasitsroleinleukocytesisnotclear.Analysisofgalectin‐12expressioninapublicdatasetofacutemyeloidleukemia(AML)samplesrevealedthatitisselectivelyoverexpressedintheM3subtype,whichisalsoknownasacutepromyelocyticleukemia(APL).Toinvestigatetheroleofgalectin‐12inAPLcells,wemanipulateditsexpressionintheAPLcellline,NB4,andmeasuredresultanteffectsonall‐trans‐retinoicacid(ATRA)–inducedgranulocyticdifferentiation.Withadoxycycline‐induciblegeneknockdownsystem,wefoundthatsuppressionofgalectin‐12promotedATRA‐inducedneutrophildifferentiationbutinhibitedlipiddropletformation.Ourresultsindicatethatoverexpressionofgalectin‐12contributestoadifferentiationblockinAPLcells,andsuppressionofgalectin‐12facilitatesgranulocyticdifferentiation.Furthermore,thesedatasuggestthatlipogenesisandotheraspectsofmyeloiddifferentiationcanbedifferentiallyregulated.Takentogether,thesefindingssuggestthatgalectin‐12maybeatargetfortreatmentoftheATRA‐resistantsubsetofAPL...

[学科分类] 生理学

[关键词] acute promyelocytic leukemia;lipid droplets;PPARγacute myeloid leukemia;myeloid differentiation