Nā huahana

ʻO ka unuhi ʻana o ka gene ABL1 i ka gene BCR ka hopena o ka oncogenic BCR-ABL1 fusion protein, kahi e hōʻike ai i ka maʻi leukemia myeloid maʻamau (CML), kahi maʻi myeloproliferative i manaʻo ʻia he make mau a hiki i ka hoʻokomo ʻana o ka ʻohana imatinib o tyrosine kinase. nā mea hoʻopaneʻe (TKI).Eia nō naʻe, ʻo ka ʻike ʻole o ka CML stem cell i ka mālama ʻana i ka TKI a me ke kūʻē ʻana a i ʻole ka loaʻa ʻana o ke kūʻē ʻana he mau kumu pinepine ia no ka hoʻomau ʻana o ka maʻi a me ka piʻi ʻana o ka pae blastic i nā maʻi ma hope o nā hoʻomaʻamaʻa kūleʻa mua.Maʻaneʻi, ua noiʻi mākou i kahi kuleana kūpono no ka MAPK15 / ERK8 kinase i ka autophagy hilinaʻi BCR-ABL1, kahi hana koʻikoʻi no ka leukemogenesis oncogene-induced.Ma kēia pōʻaiapili, ua hōʻike mākou i ka hiki o MAPK15 ke hoʻopaʻa kino i ka oncogene i nā vesicles autophagic, e hōʻoia ana i kā mākou hypothesis o kahi kuleana biologically no kēia MAP kinase i ka transduction hōʻailona e kēia oncogene.ʻOiaʻiʻo, ma ka hoʻohālikelike ʻana i ka hōʻailona BCR-ABL1 i nā cell HeLa a me ka hoʻomaikaʻi ʻana i kahi hiʻohiʻona pili physiologically no CML kanaka, ʻo ia hoʻi ʻo K562 cell, ua hōʻike mākou i ka BCR-ABL1-induced autophagy i hoʻopili ʻia e MAPK15 ma o kona hiki ke launa pū me ka ʻohana LC3. nā protein, ma kahi ʻano hilinaʻi LIR.ʻO ka mea mahalo, ua hiki nō iā mākou ke hoʻopilikia i ka autophagy i hoʻokomo ʻia e BCR-ABL1 e kahi ala lāʻau lapaʻau e pili ana i ka pale ʻana i ka MAPK15, e wehe ana i ka hiki ke hana i kēia kinase e hoʻopilikia i ka autophagy a me nā maʻi e pili ana i kēia hana cellular.ʻOiaʻiʻo, no ke kākoʻo ʻana i ka hiki o kēia ala, ua hōʻike mākou i ka pau ʻana o ka ʻōlelo MAPK15 endogenous i kāohi i ka hoʻonui ʻana o ka cell BCR-ABL1, in vitro, a me ka hoʻokumu ʻana o ka tumo, i loko o vivo, no laila e hāʻawi ana i kahi loulou "druggable" ma waena o BCR-ABL1 a kanaka CML.