{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T08:50:15Z","timestamp":1786870215821,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN2020"],"award-info":[{"award-number":["PRIN2020"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mesenchymal stromal cells (MSCs) are key components of the tumor microenvironment (TME), influencing leukemia progression through poorly understood mechanisms. Here, the bioelectrical properties of MSCs derived from pediatric acute myeloid leukemia (AML) patients (AML\u2010MSCs) are investigated, identifying a significant depolarization of their resting voltage membrane potential (V\n                    <jats:sub>mem<\/jats:sub>\n                    , \u221214.7\u00a0mV) compared to healthy MSCs (h\u2010MSCs, \u221228.5\u00a0mV), accompanied by downregulation of Calcium channel, voltage\u2010dependent, L type, alpha 1C subunit1.2 (CaV1.2) L\u2010type calcium channel expression. AML\u2010MSCs display increased spontaneous calcium oscillations, suggesting altered ion homeostasis. Notably, h\u2010MSCs exposed to AML blasts undergo a similar V\n                    <jats:sub>mem<\/jats:sub>\n                    depolarization (\u221211.8\u00a0mV) and CaV1.2 downregulation, indicating that leukemic cells actively reprogram MSCs. Functionally, V\n                    <jats:sub>mem<\/jats:sub>\n                    depolarization in h\u2010MSCs promotes a pro\u2010leukemic phenotype, whereas hyperpolarization of AML\u2010MSCs restores a normal behavior. CaV1.2 over\u2010expression by lentiviral vectors in AML\u2010MSCs shifts the V\n                    <jats:sub>mem<\/jats:sub>\n                    toward hyperpolarization and partially reverses their leukemia\u2010supportive properties, in part through CaV1.2 transfer via tunneling nanotubes. These findings reveal that AML blasts impose a bioelectrical signature on MSCs, modulating ion channel activity to sustain a leukemic niche. Targeting this electrical reprogramming through CaV1.2 restoration represents a potential strategy to re\u2010establish homeostasis in the bone marrow microenvironment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508940","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T21:44:31Z","timestamp":1755726271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Leukemic Cells Hijack Stromal Bioelectricity to Reprogram the Bone Marrow Niche via CaV1.2\u2010Dependent Mechanisms"],"prefix":"10.1002","volume":"12","author":[{"given":"Ambra","family":"Da Ros","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Benetton","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Borella","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Borile","sequence":"additional","affiliation":[{"name":"Foundation Istituto Ricerca Pediatrica Citt\u00e0 della Speranza  Padova 35127 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Cani","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Lopez\u2010Pigozzi","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy \u201cG. Galilei\u201d University of Padova  Padova 35121 Italy"},{"name":"Veneto Institute of Molecular Medicine (VIMM)  Padova 35129 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Bortolozzi","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy \u201cG. Galilei\u201d University of Padova  Padova 35121 Italy"},{"name":"Veneto Institute of Molecular Medicine (VIMM)  Padova 35129 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bresolin","sequence":"additional","affiliation":[{"name":"Foundation Istituto Ricerca Pediatrica Citt\u00e0 della Speranza  Padova 35127 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tregnago","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, IRCCS, Ospedale Pediatrico Bambino Ges\u00f9 Catholic University of the Sacred Heart  Rome 00165 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4793-5263","authenticated-orcid":false,"given":"Martina","family":"Pigazzi","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Onco\u2010Hematology lab and clinic University of Padova  Padova 35128 Italy"},{"name":"Foundation Istituto Ricerca Pediatrica Citt\u00e0 della Speranza  Padova 35127 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044414"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.08.032"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2020.0013"},{"key":"e_1_2_9_4_1","first-page":"103","volume-title":"Reviews of physiology, biochemistry and pharmacology","author":"Fan J. J.","year":"2020"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-016-1144-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/bioe.2019.0013"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00185"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.846917"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0106"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0103"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00603"},{"key":"e_1_2_9_12_1","volume":"7","author":"Carvalho\u2010de\u2010Souza J. L.","year":"2022","journal-title":"Adv. Phys."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.6341"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003737"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00251.2009"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5193(86)80209-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1935"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01496-y"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03334-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2012.0425.rev"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2016"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/bioe.2022.0001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2199"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.04.038"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-022-01189-4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-146767"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/bioe.2018.0005"},{"key":"e_1_2_9_28_1","first-page":"835","volume":"29","author":"Martins\u2010Marques T.","year":"2019","journal-title":"Biol. Funct. Connexin43 Bey.Intercell. Commun."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90438-3"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00298.2011"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00320.2006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37827"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.10.016"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010151"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207285"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.11.010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(02)00820-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(03)00202-9"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.08.011"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01022-z"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689719837897"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.07.015"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-024-01195-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/1750743X.2024.2390819"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-03941-8"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0594"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.775087"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-1069-y"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030796"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.945896"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10173790"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123191"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.05.017"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202508940","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202508940","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202508940","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:07:40Z","timestamp":1773083260000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202508940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":53,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/advs.202508940"],"URL":"https:\/\/doi.org\/10.1002\/advs.202508940","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]},"assertion":[{"value":"2025-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e08940"}}