Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5...Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5 has been reported in some cancers,such as glioma and colon cancers.However,little is known about the role of ACSL5 in acute myeloid leukemia(AML).We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors.ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients.In AML cells,the ACSL5 knockdown inhibited cell growth both in vitro and in vivo.Mechanistically,the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a.Additionally,triacsin c,a pan-ACS family inhibitor,inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199,the FDA approved BCL-2 inhibitor for AML therapy.Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.展开更多
基金supported by the key international cooperation projects of the National Natural Science Foundation of China(No.81820108004)the major projects of the Zhejiang Provincial Department of Science and Technology(No.2021C03123)the Pediatric Leukemia Diagnosis and Therapeutic Technology Research Center of Zhejiang Province(No.JBZX-201904).
文摘Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5 has been reported in some cancers,such as glioma and colon cancers.However,little is known about the role of ACSL5 in acute myeloid leukemia(AML).We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors.ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients.In AML cells,the ACSL5 knockdown inhibited cell growth both in vitro and in vivo.Mechanistically,the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a.Additionally,triacsin c,a pan-ACS family inhibitor,inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199,the FDA approved BCL-2 inhibitor for AML therapy.Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
基金supported in part by the National Natural Science Foundation of China under Grant Nos. 71171138,70871084the Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No.200806360001
文摘这篇论文从可靠性研究的观点与不可靠的加油站和多重适应推迟的假期认为排队的分离时间的 GeoX/G/1 是模型。后面的问题将被讨论：1 ) 服务者在在时间 n 的一个概括忙时期的概率；2 ) 加油站在在时间 n 的失败的概率，即，加油站的短暂 unavailability，和加油站的稳定的州的 unavailability；3 ) 加油站失败的期望的数字在时间间隔期间(0， n ] ，并且加油站的稳定的州的失败频率；4 ) 加油站故障在的期望的数字一概括的服务者忙碌时期。最后，作者证明有不可靠的加油站的一些普通分离时间的排队模型是在这篇论文讨论的模型的特殊情况。
