{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:58:53Z","timestamp":1791007133094,"version":"4.1.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"27","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,9,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Gene expression profiles were generated from bone marrow blasts at initial diagnosis from a cohort of 99 children with National Cancer Institute\u2013defined high-risk ALL who were treated uniformly on the Children's Oncology Group (COG) 1961 study. For prediction of early response, genes that correlated to marrow status on day 7 were identified on a training set and were validated on a test set. An additional signature was correlated with long-term outcome, and the predictive models were validated on three large, independent patient cohorts. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> We identified a 24\u2013probe set signature that was highly predictive of day 7 marrow status on the test set (P = .0061). Pathways were identified that may play a role in early blast regression. We have also identified a 47\u2013probe set signature (which represents 41 unique genes) that was predictive of long-term outcome in our data set as well as three large independent data sets of patients with childhood ALL who were treated on different protocols. However, we did not find sufficient evidence for the added significance of these genes and the derived predictive models when other known prognostic features, such as age, WBC, and karyotype, were included in a multivariate analysis. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Genes and pathways that play a role in early blast regression may identify patients who may be at risk for inferior responses to treatment. A fully validated predictive gene expression signature was defined for high-risk ALL that provided insight into the biologic mechanisms of treatment failure. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2007.14.4519","type":"journal-article","created":{"date-parts":[[2008,9,18]],"date-time":"2008-09-18T22:23:38Z","timestamp":1221776618000},"page":"4376-4384","source":"Crossref","is-referenced-by-count":89,"title":["Gene Expression Signatures Predictive of Early Response and Outcome in High-Risk Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study"],"prefix":"10.1200","volume":"26","author":[{"given":"Deepa","family":"Bhojwani","sequence":"first","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huining","family":"Kang","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee X.","family":"Menezes","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Yang","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harland","family":"Sather","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi P.","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Joon","family":"Min","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Potter","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Harvey","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Hunger","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita","family":"Seibel","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Raetz","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; and Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; Cancer Research and Treatment Center, University of New Mexico and Sandia National Laboratories, Albuquerque, NM; the Department of Paediatric Oncology\/Haematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam; and Department of Human Genetics, Leiden University Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[{"name":"From the New York University Cancer Institute and Division of Pediatric Hematology\/Oncology, New York University School of Medicine; 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