{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:44:47Z","timestamp":1790138687827,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,11,28]],"date-time":"2010-11-28T00:00:00Z","timestamp":1290902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Alberta Children's Hospital Research Institute for Child and Maternal Health (ACHRI); Kids Cancer Care Foundation of Alberta (KCCFA); Edward J Brown Endowment for Leukemia Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      ABT\u2010737 is a BH3 mimetic small\u2010molecule inhibitor that binds with high affinity to Bcl\u20102 to induce apoptosis in malignant cells and has shown promise as an effective anti\u2010leukemic agent in pediatric preclinical tests. This study focuses on the effects of ABT\u2010737 on leukemia cells with\n                      <jats:italic>MLL<\/jats:italic>\n                      rearrangement and identifies some of the biological correlates of its activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>Cells were cultured in the presence of increasing concentrations of ABT\u2010737 alone or in combination with other agents. After 4 days in culture, cell growth inhibition was measured by Alamar blue assay. The expression and activation of potential intracellular targets of ABT\u2010737 activity were determined by Western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant Bcl\u20102 expression was detected in all infant leukemia cells investigated. ABT\u2010737 induced cell death in all cell lines studied although the IC\n                      <jats:sub>50<\/jats:sub>\n                      values differed somewhat between cell lines. Western blot analysis identified the effects of ABT\u2010737 on survival and apoptosis\u2010regulatory proteins PARP, caspase\u20108, and cytochrome\u2010c. Drug combination studies indicated synergy with distinct anti\u2010neoplastic agents, including the multi\u2010tyrosine kinase inhibitor sunitinib. This effective drug synergy appears to be mediated by the combined inhibition of Bcl\u20102 and intracellular signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We describe the in vitro studies to demonstrate the activity and drug combinability of ABT\u2010737 against\n                      <jats:italic>MLL<\/jats:italic>\n                      rearranged leukemia cells. In addition, identification of the molecular changes that occur in the presence of ABT\u2010737 provides information regarding effective target validation and target modulation analyses in future clinical trials. Pediatr Blood Cancer 2011;56:353\u2013360. \u00a9 2010 Wiley\u2010Liss, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.22760","type":"journal-article","created":{"date-parts":[[2010,11,28]],"date-time":"2010-11-28T08:50:30Z","timestamp":1290934230000},"page":"353-360","source":"Crossref","is-referenced-by-count":20,"title":["Cytotoxicity, drug combinability, and biological correlates of ABT\u2010737 against acute lymphoblastic leukemia cells with\n                    <i>MLL<\/i>\n                    rearrangement"],"prefix":"10.1002","volume":"56","author":[{"given":"Aarthi","family":"Jayanthan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Incoronato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Blackmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Bernoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Stam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James. 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