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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3362-3367
The Presence of Typical and Atypical BCR-ABL Fusion Genes in
Leukocytes of Normal Individuals: Biologic Significance and
Implications for the Assessment of Minimal Residual Disease
Shikha Bose,
Michael Deininger,
Joanna Gora-Tybor,
John M. Goldman, and
Junia V. Melo
From the LRF Centre for Adult Leukaemia, Department of Haematology,
Imperial College School of Medicine, Hammersmith Hospital, London, UK.
The number of genetic lesions necessary to generate leukemia in
humans is unknown, but it is possible that certain specific abnormalities, eg, fusion genes, known to be associated with acute and
chronic leukemia are produced relatively frequently in human cells but
require other events to occur before the leukemia becomes manifest. We
investigated this possibility by studying peripheral blood leukocytes
from normal individuals and various hematopoietic cell lines for the
presence and expression of the p210 and the p190 types of the BCR-ABL
gene associated with chronic myeloid leukemia (CML) and acute
lymphoblastic leukemia. We used two-step reverse
transcriptase-polymerase chain reaction (RT-PCR) assays in which
batches of 108 cells per sample were tested in 40 replicate
reactions. We estimate that this assay is 1.5 logs more sensitive than
the two-step RT-PCR assays that we use routinely to assess minimal
residual disease. BCR-ABL fusion gene transcripts of various
configurations were found in circulating leukocytes from 12 of the 16 healthy adults analyzed. Transcripts with an e1a2 junction (p190
BCR-ABL) were present in 11 and p210-type transcripts with b2a2
and/or b3a2 junctions were detected in 4 individuals. The same
RT-PCR assays in non-CML cell lines showed the presence of classical or
aberrant p210-type mRNA in 3 of 7 lines and of p190-type transcripts in all 7 lines of hematopoietic origin (HL60, KG1, U937, Kasumi, Jurkat,
JVM13, and JVM25), whereas the NIH3T3 murine fibroblast line was
reproducibly negative for these fusion genes. These findings confirm
and extend previous reports on the detection of leukemia-associated genes in normal leukocytes and suggest that certain fusion genes are
generated relatively frequently in hematopoietic cells, but only
infrequently do the cells acquire the additional changes necessary to
produce leukemia in humans. Although there is only a small probability
that such innocent BCR-ABL-carrying leukocytes are detected by
conventional RT-PCR assays, they may be the source of some sporadically
positive tests in leukemia patients in long-term remission.
© 1998 by The American Society of Hematology.
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