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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2992-2996
NEOPLASIA
High frequency of leukemic clones in newborn screening
blood samples of children with B-precursor acute lymphoblastic
leukemia
Jeffrey W. Taub,
Mark A. Konrad,
Yubin Ge,
John M. Naber,
Jackie S. Scott,
Larry H. Matherly, and
Yaddanapudi Ravindranath
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.
The detection of leukemia cells on newborn genetic screening cards
("Guthrie cards") 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 "leukemic"
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 10 950/µL (range, 2900-70 300/µL) 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 "leukemic" 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 "leukemic" 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.
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