{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:33:56Z","timestamp":1773200036679,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["21 1716 Pj 01 H"],"award-info":[{"award-number":["21 1716 Pj 01 H"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["FO2022-0123"],"award-info":[{"award-number":["FO2022-0123"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lars Hiertas Minne","award":["21 1716 Pj 01 H"],"award-info":[{"award-number":["21 1716 Pj 01 H"]}]},{"name":"Lars Hiertas Minne","award":["FO2022-0123"],"award-info":[{"award-number":["FO2022-0123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) cells depend on microenvironment niches for proliferation and survival. The adhesion of tumor cells to stromal cells in such niches triggers the activation of signaling pathways crucial for their survival, including B-cell receptor (BCR) signaling. While inhibitors of Bruton\u2019s tyrosine kinase (BTKi) have shown efficacy in patients with CLL by disrupting these interactions, acquired resistance and toxicity remain a challenge during long-term therapy. Thus, identifying additional therapeutic modalities is important. Previously, we demonstrated that 5-lipoxygenase (5-LOX) pathway inhibitors reduced mantle cell lymphoma (MCL) cell adhesion to stromal cells, motivating us to investigate their potential in the context of CLL. We employed an ex vivo co-culture model to study CLL cell adhesion to stromal cells in the absence and presence of 5-LOX pathway inhibitors (zileuton and MK886) as well as the BTKi ibrutinib that was included for comparative purposes. Our findings demonstrated that different CLL samples adhere to stromal cells differentially. We observed a variable decrease in CLL cell adhesion to stromal cells following the inhibition of the 5-LOX pathway across a spectrum of patient samples that was distinct to the spectrum for ibrutinib. Positive and negative correlations were shown between the clinical and genetic features of the CLL samples and their level of adherence to stromal cells in both the absence and presence of the tested inhibitors. These results suggest the 5-LOX pathway as a candidate for assessment as a new therapeutic target in CLL.<\/jats:p>","DOI":"10.3390\/ijms26052209","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T10:12:33Z","timestamp":1740737553000},"page":"2209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Tumor Microenvironment Interactions in Chronic Lymphocytic Leukemia Using Leukotriene Inhibitors"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8157-4852","authenticated-orcid":false,"given":"Laia","family":"Sadeghi","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4165-6300","authenticated-orcid":false,"given":"Magali","family":"Merrien","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Bj\u00f6rkholm","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"\u00d6sterborg","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17176 Stockholm, Sweden"},{"name":"Department of Hematology, Karolinska University Hospital, 17176 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Erik","family":"Claesson","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-9969","authenticated-orcid":false,"given":"Anthony P. H.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.3324\/haematol.2018.200204","article-title":"First-line therapy in chronic lymphocytic leukemia: A Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013","volume":"104","author":"Sylvan","year":"2019","journal-title":"Haemiatologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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