{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:44:21Z","timestamp":1790772261321,"version":"4.1.0"},"reference-count":28,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The detection of leukemia cells on newborn genetic screening cards (\u201cGuthrie cards\u201d) of a small group of patients and several sets of identical twins developing acute lymphoblastic leukemia (ALL) with identical phenotypic and chromosomal markers has provided evidence that childhood ALL cases may arise in utero. We conducted a retrospective study of a randomly selected group of childhood B-precursor ALL patients to determine the frequency of the presence of \u201cleukemic\u201d clones prenatally in ALL cases by testing newborn screening cards. The 17 ALL patients analyzed had a median age of 46 months (range, 18 months to 13 years) and had median presenting white blood cell (WBC) counts of 10\u2009950\/\u03bcL (range, 2900-70\u2009300\/\u03bcL) at diagnosis. A clonal rearrangement of the immunoglobulin heavy chain (IgH) gene was identified in diagnostic lymphoblasts and sequenced and patient-specific primers were used to amplify DNA from blood samples on the patient's newborn screening cards. Twelve of the 17 (71%) analyzed newborn cards had detectable IgH rearrangements amplified by seminested polymerase chain reaction. DNA sequencing confirmed that the IgH rearrangements detected matched the IgH sequences identified from diagnostic leukemia cells, indicating the presence of a \u201cleukemic\u201d clone at birth. There were no differences in age or presenting WBC counts between the cases with or without positive newborn screening cards. All 6 patients with hyperdiploid ALL had detectable \u201cleukemic\u201d clones on their cards. The results of our study support the notion that a high proportion of childhood B-precursor ALL cases arise in utero, although postnatal events are also important factors in leukemogenesis.<\/jats:p>","DOI":"10.1182\/blood.v99.8.2992","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"2992-2996","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":111,"title":["High frequency of leukemic clones in newborn screening blood samples of children with B-precursor acute lymphoblastic leukemia"],"prefix":"10.1182","volume":"99","author":[{"given":"Jeffrey W.","family":"Taub","sequence":"first","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Konrad","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Ge","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Naber","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie S.","family":"Scott","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry H.","family":"Matherly","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaddanapudi","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"From the Division of Pediatric Hematology\/Oncology, Children's Hospital of Michigan, Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Michigan Department of Community Health, Lansing, MI, and Departments of Pediatrics and Pharmacology, Wayne State University School of Medicine, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217503520600_B1","first-page":"409","article-title":"Acute lymphoblastic leukemia.","volume-title":"Principles and Practice of Pediatric Oncology.","author":"Margolin","year":"1997"},{"key":"2020021217503520600_B2","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1182\/blood.V82.4.1043.bloodjournal8241043","article-title":"A natural history for pediatric acute leukemia.","volume":"82","author":"Greaves","year":"1993","journal-title":"Blood."},{"key":"2020021217503520600_B3","first-page":"3","article-title":"Epidemiology of acute leukemia in children and adults.","volume":"24","author":"Sandler","year":"1997","journal-title":"Semin Oncol."},{"key":"2020021217503520600_B4","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0140-6736(96)09412-3","article-title":"Aetiology of acute 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