P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3.
P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3.
复制标题
P2X7 通过上调 Pbx3 促进 MLL-AF9 诱导的急性髓系白血病的进展。
DOI：
10.3324/haematol.2019.243360
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发表时间：
2021-05-01
期刊：
影响因子：
10.1
通讯作者：
Zheng G
中科院分区：
文献类型：
--
作者：
Feng W;Yang X;Wang L;Wang R;Yang F;Wang H;Liu X;Ren Q;Zhang Y;Zhu X;Zheng G
核苷酸通过激活嘌呤受体介导细胞间通讯，参与多种生理和病理过程。异常的嘌呤能信号在恶性肿瘤的进展中起重要作用。P2 X7属于嘌呤能受体P2 X家族，在包括白血病在内的多种恶性肿瘤中异常表达。然而，其在白血病中的作用和分子作用机制尚未阐明。本文分析了P2 X7在急性髓系白血病（AML）中的表达与临床预后的关系，并通过小鼠AML、裸鼠移植瘤和患者来源的异种移植瘤模型探讨了P2 X7在AML进展中的作用和机制。P2 X7高表达与AML患者生存率降低相关。P2 X7在ML重排的AML中高表达，并通过促进细胞增殖和增加白血病干细胞加速这种类型的AML的进展。此外，P2 X7引起Pbx 3的上调，这可能是其促白血病作用的原因。P2 X7-Pbx 3通路也可能促进其他类型白血病以及具有高水平P2 X7表达的实体瘤的进展。我们的研究为异常嘌呤能信号传导引起的恶性肿瘤的进展提供了新的见解。
Nucleotides mediate intercellular communication by activating purinergic receptors and take part in various physiological and pathological processes. Abnormal purinergic signaling plays important roles in malignant progression. P2X7, which belongs to the P2X family of purinergic receptors, is abnormally expressed in various types of malignancies including leukemia. However, its role and molecular mechanism of action in leukemia have not been elucidated. Here, we analyzed the correlation between P2X7 expression and clinical outcome in acute myeloid leukemia (AML); we explored the role and mechanism of P2X7 in AML progression by using mouse AML, nude mouse xenograft and patientderived xenograft models. High levels of P2X7 expression were correlated with worse survival in AML. P2X7 was highly expressed in MLLrearranged AML and accelerated the progression of this type of AML both by promoting cell proliferation and by increasing leukemia stem cells. Furthermore, P2X7 caused upregulation of Pbx3 which might account for its pro-leukemic effects. The P2X7-Pbx3 pathway might also contribute to the progression of other types of leukemia as well as solid tumors with high levels of P2X7 expression. Our study provides new insights into the progression of malignancy caused by abnormal purinergic signaling.
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影响因子：
3.2
作者：
Delaporta, Polyxeni;Sofocleous, Christalena;Kattamis, Antonis
通讯作者：
Kattamis, Antonis
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
64.5
作者：
Khajuria RK;Munschauer M;Ulirsch JC;Fiorini C;Ludwig LS;McFarland SK;Abdulhay NJ;Specht H;Keshishian H;Mani DR;Jovanovic M;Ellis SR;Fulco CP;Engreitz JM;Schütz S;Lian J;Gripp KW;Weinberg OK;Pinkus GS;Gehrke L;Regev A;Lander ES;Gazda HT;Lee WY;Panse VG;Carr SA;Sankaran VG
通讯作者：
Sankaran VG
DOI：
10.1083/jcb.200405155
发表时间：
2004-11-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
McHugh B;Krause SA;Yu B;Deans AM;Heasman S;McLaughlin P;Heck MM
通讯作者：
Heck MM