Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript.
In the majority of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) patients, the c-abl gene is fused to the bcr gene, resulting in the transcription of an 8.5 kb chimeric bcr-abl mRNA, which is translated into a p210bcr-abl fusion protein. In about 50% of the Ph-positive acute lymphoid leukemias (ALL), the bcr-abl gene fusion is identical to CML, while in 50% an alternative fusion between these two genes occurs, in which the central bcr-sequences are absent. This results in transcription of a 7 kb bcr-abl mRNA, encoding a P190bcr-abl fusion protein. Cloning and sequencing of the chimeric part of bcr-abl cDNAs from two Ph-positive CML patients in chronic phase showed that in one patient, as in the Ph-positive ALL, all central bcr sequences are absent, while in the other patient, part of the bcr central sequences are deleted. Therefore, we speculate that the presence of the 7 kb chimeric ALL type mRNA in one of the patients is not sufficient to drive an acute rather than a chronic leukemic process in this case. The deletions of the central bcr-sequences described here define the minimal sequence requirement of the bcr-abl fusion gene in CML patients so far.
Selleri
L
L
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
von Lindern
M
M
Hermans
A
A
Meijer
D
D
Torelli
G
G
Grosveld
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl