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Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia.
- Source :
-
British journal of haematology [Br J Haematol] 1998 Dec; Vol. 103 (3), pp. 711-5. - Publication Year :
- 1998
-
Abstract
- The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Gene Expression
Humans
Middle Aged
RNA, Neoplasm genetics
Reverse Transcriptase Polymerase Chain Reaction methods
Alternative Splicing genetics
Fusion Proteins, bcr-abl genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1048
- Volume :
- 103
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 9858221
- Full Text :
- https://doi.org/10.1046/j.1365-2141.1998.01033.x