Nā huahana

1.Early T-cell precursor leukemia (ETP-ALL) mea he kiʻekiʻe-pilikia subtype o kanaka maʻi leukemia i poorly hoomaopopo ma ka molecular pae.Ma ʻaneʻi mākou e hōʻike nei i nā unuhi e kuhikuhi ana i ka zinc finger E-box-binding transcription factor ZEB2 ma ke ʻano he maʻi genetic recurrent i ka ʻōʻō ʻole/ETP-ALL.Ke hoʻohana nei i kahi kumu hoʻohālike ʻiole loaʻa-o-hana, hōʻike mākou i ka hoʻomau ʻana o ka Zeb2 hōʻike i hoʻomaka i ka maʻi leukemia T-cell.Eia kekahi, hōʻike ʻo Zeb2-driven mouse leukemia i kekahi mau hiʻohiʻona o ke kanaka ʻōpiopio / ETP-ALL pūlima hōʻike gen, a me ka hiki ke hoʻomaka i ka maʻi leukemia a hoʻāla ʻia ʻo Janus kinase (JAK) transcriptional activation o IL7R.Hōʻike kēia haʻawina iā ZEB2 ma ke ʻano he oncogene i loko o ka biology o ka makua ʻole / ETP-ALL a hoʻopaʻa i ke ala e hele ai i nā noiʻi pre-clinical o nā pūhui hou no ka mālama ʻana i kēia subtype koʻikoʻi o ke kanaka T-ALL me ka hoʻohana ʻana i kā mākou kumu hoʻohālike iole Zeb2.

2.Pluripotency, self-renewal, a me ka hoʻokaʻawale ʻana he mau hiʻohiʻona kūikawā o nā pūnaewele embryonic stem (ES), ma laila e hāʻawi ai i nā hiʻohiʻona waiwai i ka lāʻau lapaʻau hou.Pono nā kaʻina hana hoʻomohala i kahi hui i hoʻoponopono maikaʻi ʻia, i hoʻoponopono nui ʻia e nā ala JAK/STAT, PI3K/AKT, a me ERK/MAPK kaulana.Ua ʻike ʻia nā SPREDs (Sprouty related proteins with EVH1 domain) ma ke ʻano he inhibitors o ke ala hōʻailona ERK/MAPK, ʻoiai ʻaʻohe mea i ʻike ʻia e pili ana i kā lākou mau hana i nā cell ES a i ka wā o ka hoʻokaʻawale mua ʻana, a hiki i kēia manawa. nā pūnaewele e nānā i nā hana o nā protein SPRED i nā pūnaewele ES a i ka wā o ka hoʻokaʻawale ʻana.Hoʻonui nui ka overexpression o SPRED i ka hoʻohou hou a me ka clonogenicity o nā pūnaewele ES murine, akā ʻo ka nele o SPRED2 e hōʻemi i ka hoʻonui a hoʻonui i ka apoptosis.I ka wā o ka hoʻokaʻawale mua ʻana i nā kino embryoid, hoʻolaha nā SPRED i ke kūlana pluripotent a keʻakeʻa i ka ʻokoʻa kahi e hoʻopaneʻe nui ʻia ai ka wehe ʻana o ka mesodermal i loko o nā cardiomyocytes.Ua hōʻike ʻia ka LIF- a me ka hoʻoulu ʻana i ka ulu ʻana i nā SPRED e kāohi i ka hoʻoulu ʻana o ERK / MAPK i nā pūnaewele ES murine.Eia naʻe, ʻaʻohe hopena i ʻike ʻia ma ka LIF-induced activation o ka JAK / STAT3, a i ʻole PI3K / AKT ala ala hōʻailona e nā proteins SPRED. Hōʻike mākou e hoʻolaha ana nā SPRED i ka hoʻohou hou ʻana a kāohi i ka ʻokoʻa mesodermal o nā cell murine ES ma ke koho ʻana i ka ERK / ʻO ke ala hōʻailona MAPK i loko o nā pūnana pluripotent.