BCR-ABL as a target for novel therapeutic interventions.
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of protein tyrosine kinase activity, antisense strategies and immunomodulation.
Kindler
T
T
III. Medical Department (Hematology/Oncology), Johannes Gutenberg-University Mainz, Mainz, Germany.
Meyer
R G
RG
Fischer
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl; D016313:Genes, abl / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl