Lithibela-menin: Phekolo e Feto-fetohang bakeng sa Leukemia e Hlobaetsang ea Myeloid
Leukemia e matla ea myeloid (AML) ke kankere ea mali e rarahaneng le e fapaneng e khetholloang ke ho ata ha lisele tsa myeloid tse hlahisang myeloid. Ho sa tsotellehe tsoelo-pele ea phekolo, ho phekola AML ho ntse ho le thata, haholo-holo bakeng sa bakuli ba nang le mathata a itseng a liphatsa tsa lefutso. Lithuto tsa morao tjena li totobalitsoe koranteng. Mali li hatisa bohlokoa ba bongaka ba lithibela-mafu tsa Menin, li totobatsa bokhoni ba tsona ba ho fetola phekolo ea AML.
Karolo ea Epigenetics ho AML
Liphetoho tsa epigenetic, tse kang methylation ea DNA le phetoho ea histone, ke liphetoho tse ka fetoloang tse laolang tlhahiso ea liphatsa tsa lefutso ntle le ho fetola tatellano ea DNA. Liphetoho tsena li bapala karolo ea bohlokoa nts'etsopele ea AML. Ho shebana le mekhoa ena ea epigenetic e ka fetoloang ho fana ka mokhoa o mocha oa phekolo.
Li-Histone, liprotheine tsa bohlokoa ka har'a sephutheloana sa DNA, li fetoloa ka mor'a phetolelo joalo ka acetylation le methylation, tse susumetsang phetolelo ea liphatsa tsa lefutso. Menin, protheine ea scaffolding e kentsoeng ke liphatsa tsa lefutso tsa MEN1, e bohlokoa bakeng sa taolo ea epigenetic. E sebelisana le histone methyltransferase KMT2A le balekane ba bang ho laola tlhahiso ea liphatsa tsa lefutso. Ho AML, Menin e thusa mananeo a phetolelo ea oncogenic, haholo-holo ka ho eketsa phetoho ea liphatsa tsa lefutso tsa HOXA le MEIS1, e leng bakhanni ba bohlokoa ho AML e hlophisitsoeng bocha ea KMT2A le NPM1.
Lithibela-menin: Katleho e Kholo Kalafong ea AML
Lithibela-menin ke limolek'hule tse nyane tse khethiloeng haholo tse etselitsoeng ho sitisa tšebelisano lipakeng tsa Menin le KMT2A, ka hona li thibela litsela tsa ho ngola tse bakang oncogenic. Lithibela-mefuta tsena li bontšitse katleho e ikhethang lithutong tsa pele ho tleliniki le tsa bongaka, haholo-holo bakeng sa AML e hlophisitsoeng bocha ea KMT2A le NPM1, tseo ka kakaretso li ikarabellang bakeng sa sehlopha se seholo sa linyeoe tsa AML.
Mothibeli oa pele oa Menin, revumenib (SNDX-5613), o amohetsoe bakeng sa tšebeliso ea bongaka, 'me tse ling tse' maloa, ho kenyeletsoa ziftomenib (KO-539) le bleximenib, li ntse li etsoa liteko tsa bongaka. Teko ea AUGMENT-101 e bontšitse hore revumenib e fihletse sekhahla sa karabelo (ORR) sa 53% ho AML e khutlisetsoang morao kapa e sa laoleheng (R/R), ka litla-morao tse laolehang tse kang QTc prolongation and differentiation syndrome. Ka mokhoa o ts'oanang, liphetho tsa pele ho tsoa litekong tsa KOMET-001 le KOMET-008 tse hlahlobang ziftomenib li bontšitse sekhahla se tšepisang sa pholiso le liprofayili tsa polokeho.
Mekhoa ea phekolo ea motsoako e ntse e hlahlojoa ho ntlafatsa katleho ea lithibela-mafu tsa Menin. Lithuto tse kopanyang revumenib le li-hypomethylating agents tse kang azacitidine le venetoclax li tlalehile hore sekhahla sa karabelo se atamela 100% ho bakuli ba phetseng hantle le ba sa lokelang AML, leha ho hlokahala lithuto tse ling tse nang le lihlopha tse kholo.
Litaelo tsa Polokeho le tsa Bokamoso
Lithibela-menin ka kakaretso li bontša liprofaele tse ntle tsa polokeho, 'me litla-morao tse ngata lia laoleha ebile li ka fetoloa. Liketsahalo tse tloaelehileng tse mpe li kenyelletsa matšoao a mala, cytopenia, le differential syndrome. Litlhaloso tsa phekolo e ncha tse fanoeng ke US FDA ho revumenib le ziftomenib li totobatsa bohlokoa ba lithibela-menin ho sebetsana le litlhoko tse sa fihlellehang kalafong ea AML.
Lintlha tse tšepisang tsa bongaka mabapi le lithibela-mafu tsa Menin li tšoaea mohato o fetohang kalafong ea AML, o fanang ka tšepo ho bakuli ba nang le mefuta e fapaneng ea liphatsa tsa lefutso e phephetsang historing. Ha lipatlisiso li ntse li tsoela pele, mekhoa ena ea phekolo e ikemiselitse ho hlalosa bocha maemo a tlhokomelo bakeng sa AML.
Setsi sa Bongaka sa Machaba sa BIOOCUS se ntse se ikemiselitse ho sebelisa tsoelo-pele e tsoetseng pele joalo ka lithibela-mafu tsa Menin ho fana ka kalafo e ncha le e sebetsang bakeng sa bakuli lefatšeng ka bophara.