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Molecular characterization of 16p deletions associated with inversion 16
defines the critical fusion for leukemogenesis
P Marlton, DF Claxton, P Liu, EH Estey, M Beran, M LeBeau, JR Testa, FS Collins, JD Rowley and MJ Siciliano
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030.
The inversion of chromosome 16 [inv(16)] in acute myeloid leukemia (AML) is
associated with a p-arm deletion in a subset of patients. The inversion
results in two fusion genes: 5'-CBFB/MYH11-3' on 16p and 5'- MYH11/CBFB-3'
on 16q. We have studied cells from 42 patients with inv(16) (38 patients)
or t(16;16) (four patients) to define the frequency and characteristics of
the deletion further. Using fluorescence in situ hybridization (FISH) with
probes from cosmids, cosmid contigs, and yeast artificial chromosomes
(YACs), we found that six patients with inv(16) had a deletion of between
150 and 350 kb centromeric to the p-arm inversion breakpoint cluster region
(p-ibc). This region was shown to contain the 5' portion of the myosin
heavy chain (MYH11) gene. YACs containing the p-ibc, which had been useful
as FISH probes in the diagnosis of inv(16), detected the inversion in
deletion as well as nondeletion patient cells. Thus, the deleted region
identified in patients is entirely contained within the human genomic
content of the YACs. Southern blot experiments using probes flanking the
p-ibc indicated that the deletion removes segments within 10 kb centromeric
of the p-ibc. Reverse transcription-polymerase chain reaction (RT-PCR)
using primers from the 5' region of CBFB and the 3' region of MYH11 (distal
to the p-ibc) produced the 5'-CBFB/MYH11-3' chimeric transcript in
inv(16)/del patients. These data confirm that the 5'-CBFB/MYH11-3' chimeric
transcript, rather than the reciprocal 5'- MYH11/CBFB-3', is the critical
product for chromosome 16-related leukemogenesis.
Volume 85,
Issue 3,
pp. 772-779,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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