Specificity of BCR-ABL antisense oligonucleotides [letter; comment]

Specificity of BCR-ABL antisense oligonucleotides.

Phosphorothioate BCR-ABL antisense oligonucleotides induce cell death, but fail to reduce cellular bcr-abl protein levels.

The bcr-abl oncogene is a fusion gene resulting from a reciprocal translocation which forms the hallmark of chronic myeloid leukemia (CML). Antisense oligonucleotides complementary to the two possible mRNA breakpoints were found to inhibit cell growth of CML patient cells and cell lines, but doubt exists about their specificity. In order to test the specificity, phosphorothioate and 3' phosphor...

Specificity of ribozymes against the bcr-abl mRNAs in vitro.

Chronic myelogenous leukaemia (CML) is a disease characterized by the presence of the Philadelphia chromosome and the k r d l fusion gene, which result from a reciprocal translocation between chromosomes 9 and 22. Two forms of bcrabl mRNA exist, b3a2 and b2a2, depending upon whether the translocation includes bcr exon 3 or not. The p2 lP-*’ protein, a deregulated tyrosine kinase, is implicated ...

Managing the sequence-specificity of antisense oligonucleotides in drug discovery

All drugs perturb the expression of many genes in the cells that are exposed to them. These gene expression changes can be divided into effects resulting from engaging the intended target and effects resulting from engaging unintended targets. For antisense oligonucleotides, developments in bioinformatics algorithms, and the quality of sequence databases, allow oligonucleotide sequences to be a...

Molecular pathways: BCR-ABL.

Aberrant tyrosine kinase activity plays a critical role in many hematologic disorders, including chronic myeloid leukemia characterized by the constitutive activity of BCR-ABL. ABL therefore represents a crucial target for new therapeutic strategies. Here, we summarize the molecular pathways that are abnormally activated by the oncoprotein. Such pathways may provide additional opportunities to ...