Alaabta

Isbeddelka is-beddelka ah ee hiddo-wadaha ABL1 ee hidda-wadaha BCR waxay keentaa muujinta borotiinka fusion oncogenic BCR-ABL1, kaas oo sifeynaya bini'aadamka myeloid leukemia (CML), xanuunka myeloproliferative xanuunka loo arko inuu si aan kala go 'lahayn u dhimanayo ilaa hordhaca qoyska imatinib ee tyrosine kinase. inhibitors (TKI).Si kastaba ha ahaatee, dareen la'aanta unugyada tarma ee CML ee daaweynta TKI iyo iska caabbinta gudaha ama la helay ayaa weli ah sababaha joogtada ah ee joogtada ah ee cudurka iyo horumarka wajiga qaraxa ee la kulma bukaannada ka dib daawaynta guuleysiga bilowga ah.Halkan, waxaan ku baarnay doorka suurtagalka ah ee MAPK15/ERK8 kinase ee BCR-ABL1-ku-tiirsanaanta autophagy, habka muhiimka ah ee kansarka-induced leukemogenesis.Xaaladdan oo kale, waxaan ku tusnay awoodda MAPK15 si ay jir ahaan ugu qorto oncogene-ka xuubka 'autophagic vesicles', annagoo xaqiijinayna mala-awaalkayaga doorka bayooloji ahaan laxiriira MAP kinase ee gudbinta calaamadda oncogene-kan.Runtii, annagoo moodayna BCR-ABL1 calaamadaynta unugyada HeLa iyo ka faa'iidaysiga qaabka jir ahaaneed ee ku habboon CML bini'aadamka, ie unugyada K562, waxaan soo bandhignay in BCR-ABL1-ku-soo-baxa autophagy ay dhexdhexaadiso MAPK15 iyada oo loo marayo awoodda ay ula falgasho LC3-qoyska borotiinada, hab ku tiirsan LIR.Waxa xiiso leh, waxaan sidoo kale awoodnay inaan faragalino BCR-ABL1-ku-soo-baxa autophagy by habka dawooyinka ee loogu talagalay in la joojiyo MAPK15, furitaanka suurtagalnimada in lagu dhaqmo kinase this si ay u saameeyaan autophagy iyo cudurada ku xiran tahay shaqada gacanta.Runtii, si aan u taageerno suurtagalnimada habkan, waxaan soo bandhignay in hoos u dhaca MAPK15 muujinta endogenous MAPK15 ay joojisay kororka unugyada BCR-ABL1-ku-tiirsanaanta, in vitro, iyo samaynta burada, gudaha vivo, sidaa darteed bixinta xiriir cusub oo "druggable" ah oo u dhexeeya BCR-ABL1 iyo dadka CML.