Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. P...The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin （IL）-8 from monocytes and macrocytes. So there raises a question： whether purinoceptor P2Y6 also takes part in neuroinflammation？ Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including （1） structure of purinoceptor P2Y6; （2） distribution and properties of purinoceptor P2Y6; （3） relationships between purinoceptor P2Y6 and microglia; （4） relationships between purinoceptor P2Y6 and immunoinflammation. It＇s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.展开更多
目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上...目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上P2X嘌呤受体各亚型的表达。结果SD大鼠膀胱中的ICCs细胞主要集中于黏膜下层、肌束边缘以及肌束间,并相互连接呈网络状分布。在7种P2X嘌呤受体亚型中,ICCs细胞上可检测到P2X2和P2X5两种亚型表达。结论大鼠膀胱ICCs细胞可表达P2X2和P2X5两种嘌呤受体亚型,从功能学上证实嘌呤能信号对ICCs细胞功能有影响。展开更多
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
基金supported by the Key Scientific Research Innovation Program of Shanghai Municipal Education Commission,China (No.082260)
文摘The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin （IL）-8 from monocytes and macrocytes. So there raises a question： whether purinoceptor P2Y6 also takes part in neuroinflammation？ Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including （1） structure of purinoceptor P2Y6; （2） distribution and properties of purinoceptor P2Y6; （3） relationships between purinoceptor P2Y6 and microglia; （4） relationships between purinoceptor P2Y6 and immunoinflammation. It＇s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.
文摘目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上P2X嘌呤受体各亚型的表达。结果SD大鼠膀胱中的ICCs细胞主要集中于黏膜下层、肌束边缘以及肌束间,并相互连接呈网络状分布。在7种P2X嘌呤受体亚型中,ICCs细胞上可检测到P2X2和P2X5两种亚型表达。结论大鼠膀胱ICCs细胞可表达P2X2和P2X5两种嘌呤受体亚型,从功能学上证实嘌呤能信号对ICCs细胞功能有影响。
