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The ABL-BCR fusion gene is expressed in chronic myeloid leukemia
JV Melo, DE Gordon, NC Cross and JM Goldman
Department of Haematology, Royal Postgraduate Medical School, London, UK.
Although the BCR-ABL hybrid gene on chromosome 22q-plays a pivotal role in
the pathogenesis of chronic myeloid leukemia (CML), little is known of the
reciprocal chimeric gene, ABL-BCR, formed on chromosome 9q+. By reverse
transcription/polymerase chain reaction amplification (RT/PCR) we have
detected ABL-BCR mRNA in cells from 31 of 44 BCR-ABL positive CML patients
and 3 of 5 CML cell lines. Of the 34 positive samples, 31 had classical
t(9;22) (q34;q11) translocations; in 3 samples there was no Philadelphia
(Ph) and/or 9q+ chromosomes. ABL-BCR expression consisted of ABL(Ib)-BCR
mRNA in 26 patients and of both ABL(Ib)-BCR and ABL(Ia)-BCR mRNA species in
6 patients. The ABL-BCR transcripts encoded one or, more rarely, both of
the two potential junctions, designated ABL-b3 and ABL-b4, which differed
in size by 75 bp. In 2 patients, the BCR exon b3 was not present in either
the BCR-ABL or the corresponding ABL-BCR transcript, whereas in 5 patients
exon b3 was present in both transcripts. Direct sequencing of PCR fragments
representing the full-length coding sequence of ABL-BCR cDNAs type Ib- b3,
Ia-b3, Ib-b4, and Ia-b4 showed an open reading frame predicted to encode
fusion proteins of 370 to 414 amino-acids. If an ABL-BCR gene product is
produced in CML cells, it may be relevant as a mechanism for deregulating
the GTPase activating protein (GAP) function of BCR.
Volume 81,
Issue 1,
pp. 158-165,
01/01/1993
Copyright © 1993 by The American Society of Hematology

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