Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia.
The Philadelphia (Ph) chromosome, the product of t(9:22), is the cytogenetic hallmark of chronic myelogenous leukemia. The c-abl oncogene on chromosome 9 is translocated to the Ph chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The Ph chromosome is also found in acute lymphoblastic leukemia (Ph+ ALL). Although the c-abl is translocated and a new 190 kd c-abl protein has been identified, no breakpoints are observed in the bcr (Ph+bcr- ALL). Here we show that in Ph+bcr- ALL, breakpoints in chromosome 22 occur within the same bcr gene, but more 5' of the bcr. Cloning of a chimeric bcr-c-abl cDNA demonstrates that the fusion gene is transcribed into a 7 kb mRNA, encoding a novel fusion protein.
Hermans
A
A
Department of Cell Biology and Genetics Erasmus University, Rotterdam, The Netherlands.
Heisterkamp
N
N
von Linden
M
M
van Baal
S
S
Meijer
D
D
van der Plas
D
D
Wiedemann
L M
LM
Groffen
J
J
Bootsma
D
D
Grosveld
G
G
D001483:Base Sequence; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D007438:Introns; D007945:Leukemia, Lymphoid / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D010677:Philadelphia Chromosome; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D004247:DNA; D004262:DNA Restriction Enzymes