{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:56:32Z","timestamp":1791413792700,"version":"4.3.3"},"reference-count":42,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rituximab is a chimeric monoclonal antibody directed at CD20 with significant activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). A variety of pathways of tumor cytotoxicity different from cytotoxic chemotherapy have been proposed for this therapeutic antibody including antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. This report describes that a proportion of patients with CLL receiving rituximab treatment have in vivo activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage in blood leukemia cells immediately following infusion of rituximab. This suggests that apoptosis using a pathway similar to fludarabine and other chemotherapeutic agents is intricately involved in the blood elimination of tumor cells after rituximab treatment. Patients having caspase-3 activation and PARP cleavage in vivo had a significantly lower blood leukemia cell count after treatment as compared to those without caspase activation. Significant down-modulation of the antiapoptotic proteins XIAP and Mcl-1 was also noted, possibly explaining in part how rituximab sensitizes CLL cells to the cytotoxic effect of chemotherapy in vivo. These findings suggest that the therapeutic benefit of antibody-based therapy in vivo for patients with CLL depends in part on induction of apoptosis and provides another area of focus for studying mechanisms of antibody-resistance in neoplastic cells.<\/jats:p>","DOI":"10.1182\/blood.v99.3.1038","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"1038-1043","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":308,"title":["The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction"],"prefix":"10.1182","volume":"99","author":[{"given":"John C.","family":"Byrd","sequence":"first","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Kitada","sequence":"additional","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian W.","family":"Flinn","sequence":"additional","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Aron","sequence":"additional","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pearson","sequence":"additional","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lucas","sequence":"additional","affiliation":[{"name":"From the Division of Hematology-Oncology, The Ohio State University, Columbus; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; and Burnham Institute, Cancer Research Center, La Jolla, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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