title: Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Cell Biology and Genetics Erasmus University, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hermans
authors.forename: N
authors.initials: N
authors.lastname: Heisterkamp
authors.forename: M
authors.initials: M
authors.lastname: von Linden
authors.forename: S
authors.initials: S
authors.lastname: van Baal
authors.forename: D
authors.initials: D
authors.lastname: Meijer
authors.forename: D
authors.initials: D
authors.lastname: van der Plas
authors.forename: L M
authors.initials: LM
authors.lastname: Wiedemann
authors.forename: J
authors.initials: J
authors.lastname: Groffen
authors.forename: D
authors.initials: D
authors.lastname: Bootsma
authors.forename: G
authors.initials: G
authors.lastname: Grosveld
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger; D004247:DNA; D004262:DNA Restriction Enzymes