MOLECULAR CHARACTERIZATION OF 16P DELETIONS ASSOCIATED WITH INVERSION-16 DEFINES THE CRITICAL FUSION FOR LEUKEMOGENESIS

被引:79
作者
MARLTON, P
CLAXTON, DF
LIU, P
ESTEY, EH
BERAN, M
LEBEAU, M
TESTA, JR
COLLINS, FS
ROWLEY, JD
SICILIANO, MJ
机构
[1] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030
[2] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030
[3] NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892
[4] UNIV CHICAGO,PRITZKER SCH MED,DEPT HEMATOL ONCOL,CHICAGO,IL 60637
[5] FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111
关键词
D O I
10.1182/blood.V85.3.772.bloodjournal853772
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 1995 by The American Society of Hematology.
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页码:772 / 779
页数:8
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