{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:30:43Z","timestamp":1792218643308,"version":"4.4.0"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,8,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C&gt;T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children\u2019s Oncology Group AAML0531 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P &lt; 1.0E\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) and with lower diagnostic leukemic cell surface CD33 intensity ( P &lt; 1.0E\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P &lt; .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2016.71.2513","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T16:20:57Z","timestamp":1498234857000},"page":"2674-2682","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":151,"title":["CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children\u2019s Oncology Group Trial AAML0531"],"prefix":"10.1200","volume":"35","author":[{"given":"Jatinder K.","family":"Lamba","sequence":"first","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lata","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Loken","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda E.","family":"Ries","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. Pollard, Maine Medical Center, Portland, ME; Jessica A. Pollard, Tufts University, Boston, MA; Yi-Cheng Wang, Children's Oncology Group, Monrovia; Todd A. Alonzo, University of Southern..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Aplenc","sequence":"additional","affiliation":[{"name":"Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, WA; Jessica A. 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