Leukemia- and lymphoma-associated (LLA) chromosomal rearrangements are critical in the process of tumorigenesis. These genetic alterations are also important biological markers in the diagnosis, prognosis, and treatment of hematopoietic malignant diseases. To detect the presence or absence of these genetic alterations in healthy individuals, sensitive nested RT-PCR analyses were performed on a large number of peripheral blood samples for selected markers including MLL partial tandem duplications (PTDs), BCR-ABL p190, BCR-ABL p210, MLL-AF4, AML1-ETO, PML-RARA, and CBFB-MYH11. Using nested RT-PCR, the presence of all of these selected markers was detected in healthy individuals at various prevalence rates. No correlation was observed between incidence and age except for BCR-ABL p210 fusion, the incidence of which rises with increasing age. In addition, nested RT-PCR was performed on a large cohort of umbilical cord blood samples for MLL PTD, BCR-ABL p190 and BCR-ABL p210. The results demonstrated the presence of these aberrations in cord blood from healthy neonates. To our knowledge, the presence of PML-RARA and CBFB-MYH11 in healthy individuals has not been previously described. The present study provides further evidence for the presence of LLA genetic alterations in healthy individuals and suggests that these mutations are not themselves sufficient for malignant transformation.
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Supported in part by the Board of Regents of the State of Louisiana [grant LEQSF (2007-10)-RD-A-32 to M.L.] and developmental funds from the Tulane Cancer Center (M.L. and J.S.).
J.S., D.M., and X.H. contributed equally to this work.
