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Within this microenvironment, CLL-B-cells produce and bind cytokines, growth factors, and extracellular vesicles (EVs). In the present study, EVs purified from nurse-like cells and M2-polarized THP1 cell (M2-THP1) cultures were added to CLL-B-cells cultures. EVs were rapidly internalized by B-cells, leading to a decrease in apoptosis (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0162 and 0.0469, respectively) and an increased proliferation (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0335 and 0.0109). Additionally, they induced an increase in the resistance of CLL-B-cells to Ibrutinib, the Bruton kinase inhibitor in vitro (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0344). A transcriptomic analysis showed an increase in the expression of anti-apoptotic gene\n                    <jats:italic>BCL-2<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0286) but not\n                    <jats:italic>MCL-1<\/jats:italic>\n                    and an increase in the expression of proliferation-inducing gene\n                    <jats:italic>APRIL<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0286) following treatment with EVs. Meanwhile, an analysis of apoptotic protein markers revealed increased amounts of IGFBP-2 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0338), CD40 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0338), p53 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0219) and BCL-2 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0338). Finally, exploration of EVs protein content by mass spectrometry revealed they carry various proteins involved in known oncogenic pathways and the RNAseq analysis of CLL-B-cells treated or not with NLCs EVs show various differentially expressed genes.\n                  <\/jats:p>","DOI":"10.1038\/s41417-024-00802-7","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T15:28:21Z","timestamp":1719329301000},"page":"1164-1176","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6674-2044","authenticated-orcid":false,"given":"L\u00e9a","family":"Ikhlef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ratti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Durand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Formento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lo\u00efse","family":"Daverat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3101-8181","authenticated-orcid":false,"given":"Marie","family":"Boutaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Guillou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Dmytruk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gachard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Cosette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-8948","authenticated-orcid":false,"given":"Marie-Odile","family":"Jauberteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-5561","authenticated-orcid":false,"given":"Paul-Fran\u00e7ois","family":"Gallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"802_CR1","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1002\/ajh.26367","volume":"96","author":"M Hallek","year":"2021","unstructured":"Hallek M, Al\u2010Sawaf O. 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