{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:12Z","timestamp":1794047352541,"version":"4.8.0"},"reference-count":50,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"5","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/legalcode"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>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 in leukemia have not been elucidated. Here, we analyzed the correlation between P2X7 expression and AML clinical outcome; explored the role and mechanism of P2X7 in AML progression by using mouse acute myeloid leukemia (AML), nude mouse xenograft and patient-derived xenograft models. High levels of P2X7 expression were correlated with worse survival in AML. P2X7 was highly expressed in MLL-rearranged AML. Furthermore, P2X7 accelerated the progression of MLL-rearranged AML by both promoting cell proliferation and increasing leukemia stem cell (LSC) levels. Moreover, P2X7 caused upregulation of Pbx3 accounts 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 malignant progression caused by abnormal purinergic signaling.<\/jats:p>","DOI":"10.3324\/haematol.2019.243360","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T12:45:12Z","timestamp":1584017112000},"page":"1278-1289","source":"Crossref","is-referenced-by-count":39,"title":["P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3"],"prefix":"10.3324","volume":"106","author":[{"family":"Wenli Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Xiao Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Lina Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Rong Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Feifei Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Hao Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Xiaoli Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Qian Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Yingchi Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Xiaofan Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Guoguang Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"24705","doi-asserted-by":"crossref","unstructured":"Liu J. 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P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx. Biochem J. 2003; 374(Pt 1):51-61.","DOI":"10.1042\/bj20030585"},{"key":"24710","doi-asserted-by":"crossref","unstructured":"Chong JH, Zheng GG, Zhu XF. Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun. 2010; 391(1):498-504.","DOI":"10.1016\/j.bbrc.2009.11.087"},{"key":"24711","doi-asserted-by":"crossref","unstructured":"Zhang XJ, Zheng GG, Ma XT. Expression of P2X7 in human hematopoietic cell lines and leukemia patients. Leuk Res. 2004; 28(12):1313-1322.","DOI":"10.1016\/j.leukres.2004.04.001"},{"key":"24712","doi-asserted-by":"crossref","unstructured":"Adinolfi E, Melchiorri L, Falzoni S. P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood. 2002; 99(2):706-708.","DOI":"10.1182\/blood.V99.2.706"},{"key":"24713","doi-asserted-by":"crossref","unstructured":"Chong JH, Zheng GG, Ma YY. The hyposensitive N187D P2X7 mutant promotes malignant progression in nude mice. J Biol Chem. 2010; 285(46):36179-36187.","DOI":"10.1074\/jbc.M110.128488"},{"key":"24714","doi-asserted-by":"crossref","unstructured":"Di Virgilio F, Sarti AC, Falzoni S. Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat Rev Cancer. 2018; 18(10):601-618.","DOI":"10.1038\/s41568-018-0037-0"},{"key":"24715","doi-asserted-by":"crossref","unstructured":"Feng W, Yang F, Wang R. High level P2X7-mediated signaling impairs function of hematopoietic stem\/progenitor cells. Stem Cell Rev. 2016; 12(3):305-314.","DOI":"10.1007\/s12015-016-9651-y"},{"key":"24716","doi-asserted-by":"crossref","unstructured":"Wang R, Feng W, Wang H. Blocking migration of regulatory T cells to leukemic hematopoietic microenvironment delays disease progression in mouse leukemia model. Cancer Lett. 2020; 469:151-161.","DOI":"10.1016\/j.canlet.2019.10.032"},{"key":"24717","doi-asserted-by":"crossref","unstructured":"Wang R, Feng W, Yang F. Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia. Immunol Cell Biol. 2018; 96(2):190-203.","DOI":"10.1111\/imcb.1029"},{"key":"24718","doi-asserted-by":"crossref","unstructured":"Wang L, Feng W, Yang X. Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-kappaB and betacatenin\/ TCF signaling pathways. Cell Death Dis. 2018; 9(4):427.","DOI":"10.1038\/s41419-018-0440-1"},{"key":"24719","doi-asserted-by":"crossref","unstructured":"Yang X, Feng W, Wang R. Repolarizing heterogeneous leukemiaassociated macrophages with more M1 characteristics eliminates their proleukemic effects. Oncoimmunology. 2017; 7(4):e1412910.","DOI":"10.1080\/2162402X.2017.1412910"},{"key":"24720","doi-asserted-by":"crossref","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016; 374(23):2209-2221.","DOI":"10.1056\/NEJMoa1516192"},{"key":"24721","doi-asserted-by":"crossref","unstructured":"Meyer C, Burmeister T, Groger D. The MLL recombinome of acute leukemias in 2017. Leukemia. 2018; 32(2):273-284.","DOI":"10.1038\/leu.2017.213"},{"key":"24722","doi-asserted-by":"crossref","unstructured":"Stavropoulou V, Peters AHFM, Schwaller J. Aggressive leukemia driven by MLL-AF9. Mol Cell Oncol. 2018; 5(3):e1241854.","DOI":"10.1080\/23723556.2016.1241854"},{"key":"24723","doi-asserted-by":"crossref","unstructured":"Tsai CT, So CW. Epigenetic therapies by targeting aberrant histone methylome in AML: molecular mechanisms, current preclinical and clinical development. 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