Duplication of small segments within the major breakpoint cluster region in
chronic myelogenous leukemia
CE Litz, JS McClure, CM Copenhaver and RD Brunning
Department of Laboratory Medicine and Pathology, University of Minnesota
Medical School, Minneapolis.
The t(9;22) in chronic myelogenous leukemia (CML) may be reciprocal or, in
a minority of cases, may result in an extensive deletion of a portion of
the major breakpoint cluster region (M-bcr) of the BCR. This report
provides evidence of the duplication of small segments within the M-bcr in
a small group of patients with CML. Southern blots of Bgl II and Bgl
II/BamHI double-digested DNA from the blood or bone marrow of 46 patients
with CML were probed with a 5' 1.4-kb Taq I/HindIII M- bcr probe and a 3'
2-kb HindIII/BamHI M-bcr probe. In three patients, rearrangements were
noted with both probes in Bgl II-digested DNA, but were not present in Bgl
II/BamHI-digested DNA with either probe. Southern analysis of DNA samples
double-digested with Bgl II and BspHI from two of these three cases showed
no rearrangements with either probe; the M-bcr BspHI site is located 26 bp
3' of the BamHI site in the second intron of the M-bcr. The presence of a
rearranged M-bcr with both probes in Bgl II-digested DNA and the lack of
rearrangement in Bgl II/BamHI and Bgl II/BspHI double-digested DNA suggest
the presence of M- bcr BamHI and BspHI sites on both 9q+ chromosome (9q+)
and the Philadelphia chromosome (Ph). This implies a duplication of at
least the 26-bp M-bcr BamHI/BspHI fragment in these two samples. Sequence
data from one of these two cases confirmed the M-bcr breakpoints to be
staggered; the Ph M-bcr breakpoint occurred 258 bp downstream from the 9q+
M-bcr breakpoint. It is concluded that a duplication of small segments
within the M-bcr occurs in a small group of patients with CML, which may
lead to pseudogermline patterns on Southern blot. Such a duplication may
provide insight into the mechanism of some chromosomal translocations in
neoplasia.
Volume 81,
Issue 6,
pp. 1567-1572,
03/15/1993
Copyright © 1993 by The American Society of Hematology