{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:31:39Z","timestamp":1788535899294,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006459","name":"Children's Hospital Los Angeles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Compared to other ethnicities, Hispanics\/Latinos (H\/L) have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetic subtypes, and worse outcomes, even after correcting for socioeconomic factors. We previously demonstrated increased incidence of the high\u2010risk genetic drivers\n                      <jats:italic>IKZF1<\/jats:italic>\n                      deletion and\n                      <jats:italic>IGH::CRLF2<\/jats:italic>\n                      rearrangement in H\/L compared to non\u2010H\/L children with B\u2010ALL. Here in an expanded pediatric cohort, we sought to identify novel genetic drivers and secondary genetic alterations in B\u2010ALL associated with H\/L ethnicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      Comprehensive clinicopathologic data from patients with B\u2010ALL treated from 2016 to 2020 were analyzed. Subtype was determined from karyotype, fluorescence in situ hybridization (FISH), chromosome microarray (CMA), and our next\u2010generation sequencing (NGS) panel (OncoKids). Non\u2010driver genetic variants were also examined.\n                      <jats:italic>p<\/jats:italic>\n                      \u2010Values less than\u00a0.05 (Fisher's exact test) were considered significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among patients with B\u2010ALL at diagnosis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0273), H\/L patients (189, 69.2%) were older (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.018), more likely to present with CNS2 or CNS3 disease (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.004), and NCI high\u2010risk ALL (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.014) compared to non\u2010H\/L patients. Higher incidence of\n                      <jats:italic>IGH::CRLF2<\/jats:italic>\n                      rearrangement (B\u2010ALL, BCR::ABL1\u2010like, unfavorable;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.016) and lower incidence of\n                      <jats:italic>ETV6::RUNX1<\/jats:italic>\n                      rearrangement (favorable,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.02) were also associated with H\/L ethnicity. Among secondary (non\u2010subtype\u2010defining) genetic variants, B\u2010ALL in H\/L was associated with\n                      <jats:italic>IKFZ1<\/jats:italic>\n                      deletion alone (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.001) or with\n                      <jats:italic>IGH::CRLF2<\/jats:italic>\n                      rearrangement (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.003). The IKZF1\n                      <jats:sup>PLUS<\/jats:sup>\n                      profile (\n                      <jats:italic>IKZF1<\/jats:italic>\n                      deletion plus\n                      <jats:italic>CDKN2A\/2B<\/jats:italic>\n                      del,\n                      <jats:italic>PAX5<\/jats:italic>\n                      del, or\n                      <jats:italic>P2RY8::CRLF2<\/jats:italic>\n                      rearrangement without\n                      <jats:italic>DUX4<\/jats:italic>\n                      rearrangement) was identified as a novel high\u2010risk feature enriched in H\/L patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study shows enrichment of high\u2010risk genetic variants in H\/L B\u2010ALL and raises consideration for novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.30996","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T23:19:24Z","timestamp":1713482364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["IKZF1\n                    <sup>PLUS<\/sup>\n                    alterations contribute to outcome disparities in Hispanic\/Latino children with B\u2010lymphoblastic leukemia"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-6749","authenticated-orcid":false,"given":"Alexandra E.","family":"Kovach","sequence":"first","affiliation":[{"name":"Hematopathology, Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Keck School of Medicine of University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Wengyn","sequence":"additional","affiliation":[{"name":"Miller School of Medicine of University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-7926","authenticated-orcid":false,"given":"My H.","family":"Vu","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern California  Los Angeles California USA"},{"name":"Biostatistics Core, The Saban Research Institute Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8362-549X","authenticated-orcid":false,"given":"Andrew","family":"Doan","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern California  Los Angeles California USA"},{"name":"Cancer and Blood Disease Institute Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordana","family":"Raca","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern California  Los Angeles California USA"},{"name":"Cytogenomics, Center for Personalized Medicine, Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Bhojwani","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern California  Los Angeles California USA"},{"name":"Cancer and Blood Disease Institute Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"B\u2010lymphoblastic leukemia\/lymphoma NOS.National Cancer Institute (NCI) SEER."},{"key":"e_1_2_9_3_1","unstructured":"Cancer stat facts: leukemia \u2014 acute lymphocytic leukemia (ALL).SEER. 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