{"title":"ORP4L:靶向MCS成分能否为根除白血病提供工具?","authors":"V. Olkkonen","doi":"10.1177/2515256419840528","DOIUrl":null,"url":null,"abstract":"The study commented here reports that the OSBP homologue ORP4L is aberrantly induced in CD34+CD38− leukemia stem cells (LSCs) of patients with acute myeloid leukemia and acts as an accessory factor for phospholipase C β3 (PLCβ3), a PLC isoform with a dominant role in these cells. Our mechanistic data suggest that ORP4L extracts and presents PI4,5P2 for catalysis by PLCβ3, thus controlling Ca2+ oscillations, bioenergetics, and survival of the cells. A small molecular compound LYZ-81 is described as a specific inhibitor of ORP4L, which can be employed to eradicate LSCs in vitro and in vivo in NOD/SCID mice. Our observations identify ORP4L as a potential target for new leukemia therapies.","PeriodicalId":87951,"journal":{"name":"Contact","volume":"11 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ORP4L: Can Targeting an MCS Component Provide Tools for Eradication of Leukemia?\",\"authors\":\"V. Olkkonen\",\"doi\":\"10.1177/2515256419840528\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The study commented here reports that the OSBP homologue ORP4L is aberrantly induced in CD34+CD38− leukemia stem cells (LSCs) of patients with acute myeloid leukemia and acts as an accessory factor for phospholipase C β3 (PLCβ3), a PLC isoform with a dominant role in these cells. Our mechanistic data suggest that ORP4L extracts and presents PI4,5P2 for catalysis by PLCβ3, thus controlling Ca2+ oscillations, bioenergetics, and survival of the cells. A small molecular compound LYZ-81 is described as a specific inhibitor of ORP4L, which can be employed to eradicate LSCs in vitro and in vivo in NOD/SCID mice. Our observations identify ORP4L as a potential target for new leukemia therapies.\",\"PeriodicalId\":87951,\"journal\":{\"name\":\"Contact\",\"volume\":\"11 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Contact\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/2515256419840528\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contact","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/2515256419840528","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
ORP4L: Can Targeting an MCS Component Provide Tools for Eradication of Leukemia?
The study commented here reports that the OSBP homologue ORP4L is aberrantly induced in CD34+CD38− leukemia stem cells (LSCs) of patients with acute myeloid leukemia and acts as an accessory factor for phospholipase C β3 (PLCβ3), a PLC isoform with a dominant role in these cells. Our mechanistic data suggest that ORP4L extracts and presents PI4,5P2 for catalysis by PLCβ3, thus controlling Ca2+ oscillations, bioenergetics, and survival of the cells. A small molecular compound LYZ-81 is described as a specific inhibitor of ORP4L, which can be employed to eradicate LSCs in vitro and in vivo in NOD/SCID mice. Our observations identify ORP4L as a potential target for new leukemia therapies.
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