{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T03:39:53Z","timestamp":1792381193308,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004172","name":"Mersin \u00dcniversitesi","doi-asserted-by":"publisher","award":["2020\u20101\u2010TP2\u20104041"],"award-info":[{"award-number":["2020\u20101\u2010TP2\u20104041"]}],"id":[{"id":"10.13039\/501100004172","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Circadian clock disruption has emerged as a relevant axis in cancer; however, the expression patterns and diagnostic relevance of\n                      <jats:italic>BMAL1<\/jats:italic>\n                      and\n                      <jats:italic>CLOCK<\/jats:italic>\n                      in multiple myeloma (MM) remain insufficiently defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BMAL1<\/jats:italic>\n                      and\n                      <jats:italic>CLOCK<\/jats:italic>\n                      mRNA expression was quantified by RT\u2010qPCR in bone marrow samples from 46 newly diagnosed MM patients and 13 healthy controls. Group comparisons, ROC analyses, multivariate logistic regression, partial correlation, and machine\u2010learning models (logistic regression, random forest, and support\u2010vector machine) with stratified 5\u2010fold cross\u2010validation (including class\u2010weighted sensitivity analysis) were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BMAL1<\/jats:italic>\n                      expression was significantly higher in MM than in controls (1.12\u2009\u00b1\u20090.33 vs. 0.85\u2009\u00b1\u20090.33,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016; Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.83), whereas\n                      <jats:italic>CLOCK<\/jats:italic>\n                      showed no significant univariate difference (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.2).\n                      <jats:italic>BMAL1<\/jats:italic>\n                      demonstrated moderate diagnostic performance (AUC\u2009=\u20090.729), while\n                      <jats:italic>CLOCK<\/jats:italic>\n                      alone showed limited discrimination (AUC\u2009=\u20090.617). Combined analysis modestly improved performance (AUC\u2009=\u20090.756). In multivariate logistic regression,\n                      <jats:italic>BMAL1<\/jats:italic>\n                      remained a strong independent predictor of MM (OR\u2009=\u20093343.4,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0046), whereas\n                      <jats:italic>CLOCK<\/jats:italic>\n                      showed an inverse adjusted association (OR\u2009=\u20090.0037,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019).\n                      <jats:italic>BMAL1<\/jats:italic>\n                      and\n                      <jats:italic>CLOCK<\/jats:italic>\n                      expression were strongly correlated in MM (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009\u2248\u20090.80), persisting after adjustment for age, ISS stage, and \u03b22\u2010microglobulin (partial\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.847,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092.2\u2009\u00d7\u200910\u201313). Among classifiers, the random forest achieved the best performance (AUC\u2009=\u20090.832; AUPRC\u2009=\u20090.952). Specificity was limited across classifiers, indicating that these performance estimates are exploratory and require validation in larger cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      MM is characterized by\n                      <jats:italic>BMAL1<\/jats:italic>\n                      upregulation within a preserved but imbalanced\n                      <jats:italic>BMAL1\/CLOCK<\/jats:italic>\n                      axis rather than uniform shifts across circadian genes. Although diagnostic performance is moderate, consistent signals across statistical and machine\u2010learning approaches support an MM\u2010associated circadian expression pattern warranting further validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ijlh.70154","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:30:44Z","timestamp":1779409844000},"page":"1123-1132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circadian Deregulation in Multiple Myeloma:\n                    <i>BMAL1<\/i>\n                    \/\n                    <i>CLOCK<\/i>\n                    Expression Patterns and Diagnostic Performance"],"prefix":"10.1111","volume":"48","author":[{"given":"Hamide","family":"Albayrak","sequence":"first","affiliation":[{"name":"Health Science Institute, Department of Medical Biology Mersin University  Mersin 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