{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:53:11Z","timestamp":1781643191349,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01-CA-151837"],"award-info":[{"award-number":["U01-CA-151837"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA-154471"],"award-info":[{"award-number":["R01CA-154471"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21-CA-164098"],"award-info":[{"award-number":["R21-CA-164098"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"V-Foundation, Nautica Triathlon","award":["U01-CA-151837"],"award-info":[{"award-number":["U01-CA-151837"]}]},{"name":"V-Foundation, Nautica Triathlon","award":["R01CA-154471"],"award-info":[{"award-number":["R01CA-154471"]}]},{"name":"V-Foundation, Nautica Triathlon","award":["R21-CA-164098"],"award-info":[{"award-number":["R21-CA-164098"]}]},{"name":"Ronald McDonald House Charities of Southern California","award":["U01-CA-151837"],"award-info":[{"award-number":["U01-CA-151837"]}]},{"name":"Ronald McDonald House Charities of Southern California","award":["R01CA-154471"],"award-info":[{"award-number":["R01CA-154471"]}]},{"name":"Ronald McDonald House Charities of Southern California","award":["R21-CA-164098"],"award-info":[{"award-number":["R21-CA-164098"]}]},{"name":"William Lawrence, Blanche Hughes Foundation grant","award":["U01-CA-151837"],"award-info":[{"award-number":["U01-CA-151837"]}]},{"name":"William Lawrence, Blanche Hughes Foundation grant","award":["R01CA-154471"],"award-info":[{"award-number":["R01CA-154471"]}]},{"name":"William Lawrence, Blanche Hughes Foundation grant","award":["R21-CA-164098"],"award-info":[{"award-number":["R21-CA-164098"]}]},{"name":"Ares Pharmaceuticals","award":["U01-CA-151837"],"award-info":[{"award-number":["U01-CA-151837"]}]},{"name":"Ares Pharmaceuticals","award":["R01CA-154471"],"award-info":[{"award-number":["R01CA-154471"]}]},{"name":"Ares Pharmaceuticals","award":["R21-CA-164098"],"award-info":[{"award-number":["R21-CA-164098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>We previously reported a splicing defect (CD22\u0394E12) associated with the deletion of exon 12 of the inhibitory co-receptor CD22 (Siglec-2) in leukemia cells from patients with CD19+ B-precursor acute lymphoblastic leukemia (B-ALL). CD22\u0394E12 causes a truncating frameshift mutation and yields a dysfunctional CD22 protein that lacks most of the cytoplasmic domain required for its inhibitory function, and it is associated with aggressive in vivo growth of human B-ALL cells in mouse xenograft models. Although CD22\u0394E12 with selective reduction of CD22 exon 12 (CD22E12) levels was detected in a high percentage of newly diagnosed as well as relapsed B-ALL patients, its clinical significance remains unknown. We hypothesized that B-ALL patients with very low levels of wildtype CD22 would exhibit a more aggressive disease with a worse prognosis because the missing inhibitory function of the truncated CD22 molecules could not be adequately compensated by competing wildtype CD22. Here, we demonstrate that newly diagnosed B-ALL patients with very low levels of residual wildtype CD22 (\u201cCD22E12low\u201d), as measured by RNAseq-based CD22E12 mRNA levels, have significantly worse leukemia-free survival (LFS) as well as overall survival (OS) than other B-ALL patients. CD22E12low status was identified as a poor prognostic indicator in both univariate and multivariate Cox proportional hazards models. CD22E12low status at presentation shows clinical potential as a poor prognostic biomarker that may guide the early allocation of risk-adjusted, patient-tailored treatment regimens and refine risk classification in high-risk B-ALL.<\/jats:p>","DOI":"10.3390\/cancers15051599","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T02:06:43Z","timestamp":1678068403000},"page":"1599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CD22 Exon 12 Deletion as an Independent Predictor of Poor Treatment Outcomes in B-ALL"],"prefix":"10.3390","volume":"15","author":[{"given":"Sanjive","family":"Qazi","sequence":"first","affiliation":[{"name":"Ares Pharmaceuticals, Saint Paul, MN 55110, USA"},{"name":"Division of Hematology-Oncology, Department of Pediatrics and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-183X","authenticated-orcid":false,"given":"Fatih M.","family":"Uckun","sequence":"additional","affiliation":[{"name":"Ares Pharmaceuticals, Saint Paul, MN 55110, USA"},{"name":"Division of Hematology-Oncology, Department of Pediatrics and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1042\/BST0361467","article-title":"Siglecs as positive and negative regulators of the immune system","volume":"36","author":"Crocker","year":"2008","journal-title":"Biochem. 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