Original Article
Leukemia (2008) 22, 1692–1697; doi:10.1038/leu.2008.152; published online 12 June 2008
Acute Leukemias
Prenatal origin of childhood acute lymphoblastic leukemia, association with birth weight and hyperdiploidy
B Gruhn1, J W Taub2, Y Ge2, J F Beck1, R Zell3, R Häfer1, F H Hermann4, K-M Debatin5 and D Steinbach5
- 1Department of Pediatrics, University Children's Hospital Jena, University of Jena, Jena, Germany
- 2Children's Hospital of Michigan, Wayne State University, Detroit, MI, USA
- 3Institute for Virology and Antiviral Therapy, University of Jena, Jena, Germany
- 4Institute of Human Genetics, University of Greifswald, Greifswald, Germany
- 5Department of Pediatrics, University of Ulm, Ulm, Germany
Correspondence: Dr B Gruhn, Department of Pediatrics, University Children's Hospital Jena, Jena 07740, Germany. E-mail: bernd.gruhn@med.uni-jena.de; Dr D Steinbach, Department of Pediatrics, University Children's Hospital Ulm, Eythstrasse 24, Ulm 89075, Germany. E-mail: Daniel@Steinba.ch
Received 8 May 2008; Accepted 15 May 2008; Published online 12 June 2008.
Abstract
Recent studies with very small numbers of patients showed that in some cases of childhood acute lymphoblastic leukemia (ALL), preleukemic cells are detectable on Guthrie cards that were used for newborn screening. We present here the largest series of ALL patients (n=32) in whom Guthrie cards were analyzed for the presence of preleukemic cells. Rearranged immunoglobulin heavy-chain genes were used as a marker for leukemic clones. We combined our set of patients with 17 previously published cases. Preleukemic cells were detected in 31 of all 49 patients (63%). Positive screening cards were not associated with patient's age at diagnosis but were almost always found in patients with hyperdiploidy (10/11; 91%; P=0.04). High birth weight is an established risk factor for childhood ALL. Positive screening cards were strongly associated with low birth weight (P=0.01). In conclusion, the majority of childhood B-precursor ALL arise prior to birth. In the search for causes of childhood leukemia we should concentrate on prenatal factors as well as postnatal factors. Our results suggest that autologous cord bloods could be a poor choice as the source of stem cells for transplantation in leukemia, which may contain preleukemic cells. Pending the development of suitable methods, childhood leukemia is a potentially screenable disease.
Keywords:
Guthrie cards, acute lymphoblastic leukemia, minimal residual disease
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