bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia.
The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5' bcr sequences could be demonstrated, but the corresponding translocated 3' bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c-abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1-positive CML patients investigated in chronic and acute states.
De Klein
A
A
Hagemeijer
A
A
Bartram
C R
CR
Houwen
R
R
Hoefsloot
L
L
Carbonell
F
F
Chan
L
L
Barnett
M
M
Greaves
M
M
Kleihauer
E
E
D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000235:genetics; D005796:Genes; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics*; D010677:Philadelphia Chromosome; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm