Rearrangement of the breakpoint cluster region and expression of P210
BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid
leukemia
CM Price, F Rassool, MK Shivji, J Gow, CJ Tew, C Haworth, JM Goldman and LM Wiedemann
Department of Haematology, Charing Cross and Westminster Medical School,
London, England.
The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in
chronic myeloid leukemia (CML) but is less common in acute lymphoblastic
leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of
CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is
translocated to the breakpoint cluster region (bcr) of the BCR gene at
22q11 to form a chimeric gene encoding a novel 210-kd protein (P210
BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+
ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the
BCR gene; this results in a smaller chimeric gene which encodes a P190
BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a
"masked" Ph chromosome in association with extensive karyotypic changes.
The leukemic cells initially showed rearrangement of the bcr, presence of a
hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent
in remission. These results support the concept that the BCR-ABL chimeric
gene plays a crucial role in leukemogenesis but suggest that factors other
than the position of the breakpoint in the BCR gene determine the lineage
of the target cell for malignant transformation.
Volume 72,
Issue 5,
pp. 1829-1832,
11/01/1988
Copyright © 1988 by The American Society of Hematology
