{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:29Z","timestamp":1760166629868,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-65\/2024-03\/200113","46","56"],"award-info":[{"award-number":["451-03-65\/2024-03\/200113","46","56"]}]},{"name":"Faculty of Medicine University of Nis, Serbia Internal projects","award":["451-03-65\/2024-03\/200113","46","56"],"award-info":[{"award-number":["451-03-65\/2024-03\/200113","46","56"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background: A dysregulated proinflammatory microenvironment is considered one of the reasons why current therapies of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI) do not secure disease control. Therefore, the development of BCR-ABL1-independent therapies is encouraged. Renalase (RNLS) is a multifunctional protein that exhibits both enzymatic and non-enzymatic cytokine-like properties, along with potent anti-inflammatory and anti-apoptotic effects. It is expressed in various tissues, including tumors. Methods: We investigated the levels of RNLS in the blood of CML patients in the chronic phase, treatment na\u00efve patients, and those in remission under TKI treatment (either imatinib or nilotinib) and compared them to healthy individuals. Results: Renalase concentration was markedly decreased in treatment-naive CML patients compared to other groups (p = 0.000), while lower levels in the TKI group were not statistically significant compared to controls. The levels correlated negatively with the total leukocyte and neutrophil count (p &lt; 0.05), while a positive correlation was present with CRP levels in treatment na\u00efve patients. Conclusions: Dynamic regulation of RNLS expression and activity is coupled with transcription factors NF-\u03baB and STAT3. Interpretation of our results might rely on differential requirements of activated STATs (STAT3\/5) during CML clone development and maintenance, including the observation of RNLS rise upon TKI introduction. Overall, our research provides new insights into the field of hematological malignancies. Unlike other malignancies studied, RNLS plasma levels are significantly decreased in CML. In future perspectives, RNLS could potentially serve as a diagnostic, prognostic, or therapeutic option for these patients.<\/jats:p>","DOI":"10.3390\/pathophysiology31040053","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T11:17:20Z","timestamp":1733829440000},"page":"787-796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low Renalase Levels in Newly Diagnosed CML: Dysregulation Sensitive to Modulation by Tyrosine Kinase Inhibitors"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-0109","authenticated-orcid":false,"given":"Jelena","family":"Milenkovic","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, University of Nis, Faculty of Medicine, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dijana","family":"Stojanovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Nis, Faculty of Medicine, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanja","family":"Velickovic","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Allergology and Clinical Immunology, University Clinical Center in Nis, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Djordjevic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Nis, Faculty of Medicine, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-5774","authenticated-orcid":false,"given":"Goran","family":"Marjanovic","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Allergology and Clinical Immunology, University Clinical Center in Nis, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2394-2757","authenticated-orcid":false,"given":"Maja","family":"Milojkovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Nis, Faculty of Medicine, 18000 Nis, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fisher, D.A.C., Fowles, J.S., Zhou, A., and Oh, S.T. 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