BCR-ABL: an anti-apoptosis gene in chronic myelogenous leukemia.
The expression of bcr-abl in chronic myelogenous leukemia leads to a large increase in the generation of mature myeloid cells. The key biochemical alteration in this disease is an increased Abl kinase activity. This up-regulation in activity is mediated through the binding of a portion of the Bcr molecule to the SH2 regulatory domain of the Abl protein. One effect of this alteration is a marked increase in resistance to drug induced cell death by apoptosis. This resistance can be overcome with the use of appropriate antisense oligonucleotides to the bcr-abl gene. The role and contribution of apoptosis to the development of the disease and the prospect of using antisense oligonucleotides as therapeutic agents is discussed.
Department of Biochemistry, University College, Cork, Ireland.
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Cotter
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D011519:Proto-Oncogenes
D016376:Oligonucleotides, Antisense