Antisense therapeutics in chronic myeloid leukaemia: the promise, the progress and the problems.
DNA sequences which are complementary or 'antisense' to a target mRNA can inhibit expression of that mRNA's protein product. Antisense therapeutics has therefore received attention for inhibiting oncogenes in haematological malignancy, in particular in chronic myeloid leukaemia. However, it is now becoming clear that antisense therapeutics is considerably more problematic than was naively initially assumed. In this article, some of these difficulties are discussed, together with the achievements in CML so far. Considerable further research is required in order to define an optimal antisense therapeutics strategy for clinical use.
Clark
R E
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University Department of Haematology, Royal Liverpool University Hospital, UK.
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D003851:Deoxyribonucleases / Q000502:physiology; D005544:Forecasting; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000235:genetics; D016896:Treatment Outcome
D016375:Antisense Elements (Genetics); D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl; D003851:Deoxyribonucleases