{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:19:28Z","timestamp":1791404368433,"version":"4.3.3"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Multiple myeloma (\n                      <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                      ) is a blood cancer marked by the abnormal clonal growth of plasma cells. Hypoxia plays a critical role in the progression and treatment resistance of\n                      <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study investigates the expression of B\u2010cell\/CLL lymphoma 2 (BCL2) family genes. We also investigated the activity of BCL2 and exportin\u20101 (XPO1) inhibitors and the potential therapeutic synergy of venetoclax and selinexor under hypoxic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Analysis of publicly available datasets revealed hypoxia\u2010induced upregulation of\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>BCL2<\/jats:italic>\n                      <\/jats:styled-content>\n                      and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">BCL2<\/jats:styled-content>\n                        \u2010like 11\n                      <\/jats:italic>\n                      (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">BCL2L11<\/jats:styled-content>\n                        )\n                      <\/jats:italic>\n                      , while\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">BCL2<\/jats:styled-content>\n                        \u2010associated agonist of cell death (\n                        <jats:styled-content style=\"fixed-case\">BAD<\/jats:styled-content>\n                        )\n                      <\/jats:italic>\n                      expression was suppressed. Venetoclax, a selective\n                      <jats:styled-content style=\"fixed-case\">BCL2<\/jats:styled-content>\n                      inhibitor, demonstrated enhanced cytotoxicity and increased caspase\u20103\/7 activity under hypoxic conditions. Selinexor exhibited potent anti\u2010myeloma effects, including dose\u2010dependent reductions in cell viability and increased apoptotic activity. Combining selinexor with venetoclax under hypoxia produced anti\u2010myeloma effects, significantly reducing cell viability, increasing apoptosis, and disrupting the mitochondrial membrane potential. This combination effectively overcame resistance in bortezomib\u2010resistant\n                      <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                      cells and demonstrated efficacy in primary plasma cell leukemia (\n                      <jats:styled-content style=\"fixed-case\">PCL<\/jats:styled-content>\n                      ) samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the potential of selinexor and venetoclax combination therapy to exploit hypoxia\u2010induced vulnerabilities in MM cells.<\/jats:p>\n                  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