{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T19:52:02Z","timestamp":1783626722347,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T00:00:00Z","timestamp":1697932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2009\/51002\u20108"],"award-info":[{"award-number":["2009\/51002\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p><jats:bold>Background<\/jats:bold>: The mitogen\u2010activated protein kinase (MAPK)\/ERK signaling cascade and the phosphoinosytol\u20103 phosphate\/Akt (PI3K\/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K\/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Aims<\/jats:bold>: To assess the activity and prognostic implications of MAPK\/ERK and PI3K\/Akt pathways in adult (ALL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined 28 precursor\u2010B\u2010cell ALL and 6 T\u2010cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten out of 15 (67%) ALL fresh samples (7 B\u2010cell, 3 T\u2010cell) showed constitutive p\u2010ERK expression. The p\u2010ERK mean fluorescent index ratio (MFI (<jats:italic>R<\/jats:italic>)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74\u20133.10] vs. 1.08 [1.02\u20131.21], respectively [<jats:italic>p<\/jats:italic>\u2009=\u2009.069]) and was significantly lower than in leukemic cell lines (median MFI (<jats:italic>R<\/jats:italic>) 3.83 [3.71\u20135.97] [<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001]). Expression of p\u2010Akt was found in 35% (12\/34) (10 B\u2010cell, 2 T\u2010cell). The median MFI (<jats:italic>R<\/jats:italic>) expression for p\u2010Akt in primary blast cell was 1.13 (0.48\u20139.90) compared to 1.01 (1.00\u20131.20) in normal T lymphocytes (<jats:italic>p<\/jats:italic>\u2009=\u2009ns) and lower than in leukemic cell lines (median MFI (<jats:italic>R<\/jats:italic>) 2.10 [1.77\u20133.40] [<jats:italic>p<\/jats:italic>\u2009=\u2009.037]). Moreover, expression of p\u2010ERK was negatively associated with the expression of CD34 (1.22 [0.74\u20131.33] vs. 1.52 [1.15\u20133.10] for CD34(+) and CD34(\u2212) group, respectively, <jats:italic>p<\/jats:italic>\u2009=\u2009.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that both MAPK\/ERK and PI3K\/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1912","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T05:25:06Z","timestamp":1698038706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>MAPK<\/scp>\/<scp>ERK<\/scp> and <scp>PI3K<\/scp>\/<scp>AKT<\/scp> signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-2273","authenticated-orcid":false,"given":"Gustavo","family":"Loureiro","sequence":"first","affiliation":[{"name":"Division of Hematology Universidade Federal de S\u00e3o Paulo (EPM\u2010UNIFESP)  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella M.","family":"Bahia","sequence":"additional","affiliation":[{"name":"Division of Hematology Universidade Federal de S\u00e3o Paulo (EPM\u2010UNIFESP)  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lucia M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Instituto de Oncologia Pedi\u00e1trica Grupo de Apoio ao Adolescente e a Crian\u00e7a com C\u00e2ncer (GRAACC)  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mair Pedro","family":"de Souza","sequence":"additional","affiliation":[{"name":"Division of Hematology Hospital Amaral Carvalho  Ja\u00fa S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza Y. 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