{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:45:23Z","timestamp":1760985923401,"version":"3.40.5"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["AIRC 5x1000 Ref. 21147 (AB) \u2010","AIRC IG 2017 (AB) \u2010","MFAG\u20102009(LLN)"],"award-info":[{"award-number":["AIRC 5x1000 Ref. 21147 (AB) \u2010","AIRC IG 2017 (AB) \u2010","MFAG\u20102009(LLN)"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The PI3K\/Akt\/mTOR (PI3K) signaling pathway has a crucial role in T\u2010cell acute lymphoblastic leukemias (T\u2010ALLs). Although loss\u2010of\u2010function of phosphatase and tensin homolog (PTEN) is a common event in pediatric T\u2010ALLs, the exact role of this tumor suppressor in T\u2010ALL development has yet to be defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we report an optimized cytometric method for accurate proteomic profiling of T\u2010ALL leukemic blasts at single\u2010cell level. We determined the expression of PI3K and JAK\u2013STAT signaling components in both primary and immortalized T\u2010ALL cells as well as in normal T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that <jats:italic>PTEN<\/jats:italic> exon 7 mutated T\u2010ALL cells retain a distinct PI3K activation; in particular, these cells show higher pAkt levels and a lower pS6 expression. Interestingly, we demonstrated for the first time that <jats:italic>PTEN<\/jats:italic> exon 7 mutated T\u2010ALL are nonresponsive to IL7 in vitro as assessed by lack of pSTAT5 activation, although they do express IL7R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Phosphoflow analysis represents a fast, reliable, and accurate method to study the signaling profile of T\u2010ALL. <jats:italic>PTEN<\/jats:italic> exon 7 mutated T\u2010ALL cells are nonresponsive to IL7 in vitro suggesting that they may activate other mechanisms to support their viability and proliferation such as a higher constitutive PI3K\/Akt signaling. Further investigations are necessary to elucidate the significance of this peculiar signaling behavior. Our observations should be taken into account in future studies aiming at molecular targeting of PI3K and\/or JAK\/STAT pathways for pharmacological intervention in T\u2010ALL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cyto.b.21882","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T15:50:42Z","timestamp":1591026642000},"page":"491-503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Single\u2010cell profiling of pediatric T\u2010cell acute lymphoblastic leukemia: Impact of <scp><i>PTEN<\/i><\/scp> exon 7 mutation on <scp>PI3K<\/scp>\/<scp>Akt<\/scp> and <scp>JAK\u2013STAT<\/scp> signaling pathways"],"prefix":"10.1002","volume":"98","author":[{"given":"Paola","family":"Bonaccorso","sequence":"first","affiliation":[{"name":"M. Tettamanti Research Center University of Milano\u2010Bicocca, San Gerardo Hospital  Monza Italy"},{"name":"Center of Pediatric Hematology Oncology Azienda Policlinico\u2010OVE, University of Catania  Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-7097","authenticated-orcid":false,"given":"Cristina","family":"Bugarin","sequence":"additional","affiliation":[{"name":"M. Tettamanti Research Center University of Milano\u2010Bicocca, San Gerardo Hospital  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Buracchi","sequence":"additional","affiliation":[{"name":"M. Tettamanti Research Center University of Milano\u2010Bicocca, San Gerardo Hospital  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazia","family":"Fazio","sequence":"additional","affiliation":[{"name":"M. Tettamanti Research Center University of Milano\u2010Bicocca, San Gerardo Hospital  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"M. Tettamanti Research Center University of Milano\u2010Bicocca, San Gerardo Hospital  Monza Italy"},{"name":"Pediatric Clinic University of Milano Bicocca, Fondazione MBBM\/Ospedale San Gerardo  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-1799","authenticated-orcid":false,"given":"Luca","family":"Lo Nigro","sequence":"additional","affiliation":[{"name":"Center of Pediatric Hematology Oncology Azienda Policlinico\u2010OVE, University of Catania  Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Gaipa","sequence":"additional","affiliation":[{"name":"M. 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