{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:20:10Z","timestamp":1788466810511,"version":"build-2803163510"},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>WHO5 (2022) classification of B-lymphoblastic leukemia (B-ALL) incorporates several novel entities requiring high-throughput sequencing for their accurate characterization. The clinical relevance of this classification in the context of contemporary measurable residual disease (MRD)\u2013directed therapy is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed 533 pediatric B-ALL uniformly treated with Indian Collaborative Childhood Leukaemia group (ICiCLe)-ALL-14 protocol as defined by WHO-2016 and reclassified them as per WHO5 using targeted sequencing, FISH, and cytogenetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Subtype-defining genomic abnormalities were identified in 81.2% of the cohort as per the WHO5 classification. Among the new subtypes,\n                      <jats:italic toggle=\"yes\">PAX5<\/jats:italic>\n                      <jats:sup>alt<\/jats:sup>\n                      and\n                      <jats:italic toggle=\"yes\">MEF2D<\/jats:italic>\n                      -r were associated with a trend toward an inferior 3-year event-free survival (EFS) of 32.8% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .003) and 33.7% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .091), respectively. We developed a three-tier genomic risk stratification model incorporating 15 genomic subtypes and the\n                      <jats:italic toggle=\"yes\">IKZF1<\/jats:italic>\n                      deletion. Children with standard (SGR), intermediate (IGR), and high genomic risk (HGR) demonstrated 3-year EFS of 80.4%, 59.3%, and 45.8% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001), and 3-year overall survival of 89.6%, 75.3%, and 62.3% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001), respectively. Genomic risk further identified heterogeneous outcomes among ICiCLe risk groups (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). SGR was associated with superior EFS irrespective of MRD status (3-year EFS 80.5% in postinduction [PI] MRD\u2013negative\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      80.8% PI-MRD\u2013positive patients,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .530). On multivariable analysis, genomic risk (hazard ratio [HR], 1.7 [95% CI, 1.41 to 2.01];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001), initial ICiCLe risk (HR, 1.3 [95% CI, 1.06 to 1.49];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .009), and PI-MRD (HR, 2.2 [95% CI, 1.66 to 2.90];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001) independently predicted EFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The study demonstrates the potential role of genomic risk stratification, in conjunction with MRD, in stratifying patients into clinically relevant risk categories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/go-25-00665","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:59:11Z","timestamp":1788465551000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Relevance of Genomics Defined WHO5 Subtypes of Pediatric B-ALL in the Context of Measurable Residual Disease\u2013Directed Risk-Based Therapy"],"prefix":"10.1200","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-4674","authenticated-orcid":true,"given":"Sweta","family":"Rajpal","sequence":"first","affiliation":[{"name":"Department of Haematopathology, ACTREC, Tata Memorial Centre, Navi Mumbai, India"},{"name":"Homi Bhabha National Institute (HBNI), Mumbai, 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