Preleukemic TEL-AML1–positive Clones at Cell Level of 10−3... : Journal of Pediatric Hematology/Oncology (original) (raw)

Original Articles

Preleukemic _TEL-AML1_–positive Clones at Cell Level of 10−3 to 10−4 do not Persist into Adulthood

Olsen, Marianne MD* †; Madsen, Hans O. MSc†; Hjalgrim, Henrik MD, PhD‡; Gregers, Jannie CLS*; Rostgaard, Klaus MSc‡; Schmiegelow, Kjeld MD*

*Section of Pediatric Hematology and Oncology, Pediatric Clinic II, Juliane Marie Center

†Tissue Typing Laboratory, Department of Clinical Immunology, Copenhagen University Hospital, H:S Rigshospitalet

‡Department of Epidemiologic Research, Division of Epidemiology, Statens Serum Institute, Copenhagen, Denmark

Supported by the Danish Children's Cancer Foundation, the Novo Nordisk Foundation, Danish Cancer Research Foundation, the Otto Christensen Foundation, and the Heine Hoi Foundation.

Reprints: Marianne Olsen, MD, Copenhagen University Hospital Rigshospitalet, Juliane Marie Center, Bonkolab-5704, Blegdamsvej 9, 2100 Copenhagen, Denmark (e-mail: [email protected]).

Received for publication March 23, 2006; accepted September 6, 2006

Abstract

The TEL-AML1 translocation, t(12;21)(p13;q22), is one of the most frequent genetic aberrations in childhood B-cell precursor acute lymphoblastic leukemia (ALL), where it occurs in 25% of all cases. In contrast, the translocation is seen in only 3% of adult ALL cases. Evidence suggests that the TEL-AML1 translocation occurs in utero in 1% of all newborn children at cell levels of 10−3 to 10−4. In this study, we explore the prevalence of _TEL-AML1_–positive cells in 2 cohorts of healthy blood donors by real-time and nested reverse transcription-polymerase chain reaction. Overall, _TEL-AML1_–positive cells were demonstrated in 10 of 2005 healthy donors, that is, a prevalence of 0.5% (95% confidence interval, 0.2-0.3%). The level of _TEL-AML1_–positive cells was estimated to 10−5 to 10−6. The observed prevalence of _TEL-AML1_–positive cells in healthy adults is of the same order of magnitude as the prevalence reported in healthy newborns, but the observed cell level of 10−5 to 10−6 is much lower. These data indicates that prenatal TEL-AML1 subclones does not persist throughout adult life at cell levels of 10−3 to 10−4. The findings are compatible with the risk of t(12;21)(p13;q22) ALL correlating with the total number of _TEL-AML1_–positive cells in peripheral blood in both childhood and adulthood.