{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:38:59Z","timestamp":1782376739122,"version":"3.54.5"},"reference-count":121,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It is characterized by the clonal proliferation of mature B cells. The tumor microenvironment (TME) seems to play a crucial role in the survival and proliferation of tumor cells. Multiple new classes of drugs had been approved for the management of patients with CLL, reshaping the treatment paradigm. The most important classes are Bruton\u2019s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. Both of them are approved as a first-line treatment in patients with CLL requiring treatment. The role of BTK and BCL-2 in the signaling pathways of the TME is very important. The aim of this review is to summarize the major components of the TME and the available data regarding targeted therapies in CLL.<\/jats:p>","DOI":"10.3390\/cimb47080604","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T08:46:55Z","timestamp":1754383615000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-2202","authenticated-orcid":false,"given":"Khalil","family":"Saleh","sequence":"first","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7015-0448","authenticated-orcid":false,"given":"Ahmadreza","family":"Arbab","sequence":"additional","affiliation":[{"name":"Department of Biopathology, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Khalife","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2696-3580","authenticated-orcid":false,"given":"Rita","family":"Khoury","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3928-6161","authenticated-orcid":false,"given":"Mohamad Ali","family":"Hachem","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Khalil","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cendrella","family":"Bou Orm","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joud","family":"Sawan","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Lafarge","sequence":"additional","affiliation":[{"name":"Department of Biopathology, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nohad","family":"Masri","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zamzam","family":"Tikriti","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Chahine","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Le Cesne","sequence":"additional","affiliation":[{"name":"International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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