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BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual
granulocyte-macrophage colony-forming unit colonies derived from blood of
patients with chronic myeloid leukemia
J Diamond, JM Goldman and JV Melo
Department of Haematology, Royal Postgraduate Medical School, London, UK.
It has been suggested that the BCR-ABL gene of chronic myeloid leukemia
(CML) is not uniformly expressed in Philadelphia (Ph)-positive cells, and
that BCR-ABL gene expression precludes transcription of the normal BCR or
ABL genes. Therefore, we have analyzed granulocyte-macrophage
colony-forming unit (CFU-GM) colonies derived from peripheral blood of 11
CML patients by cytogenetic and by reverse transcriptase-polymerase chain
reaction (PCR) amplification of BCR-ABL, ABL-BCR, BCR, and ABL. All CFU-GM
colonies with analyzable metaphases were found to contain a Ph chromosome.
In 2 patients, the initial PCR screening failed to detect BCR-ABL
transcripts in 2 of 11 and 1 of 7 Ph-positive colonies. However, when
amplification for BCR-ABL was repeated in quintuplicate, all but 1 colony
from a single patient showed one or more positive results. Amplifications
of the four genes in each colony showed that BCR-ABL, ABL-BCR, and the
normal BCR and ABL were simultaneously expressed in the majority of CFU-GM
colonies. Replicate PCR tests for BCR and for ABL in colonies initially
scored as negative also uncovered previously undetected positive
amplifications. We conclude that BCR-ABL expression does not suppress
transcription from the normal BCR and ABL genes, and that Ph-positive,
BCR-ABL-negative colonies derived from peripheral blood CFU-GM are rare or
nonexistent.
Volume 85,
Issue 8,
pp. 2171-2175,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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