title: A small molecule significantly inhibits the bcr/abl fusion gene at the mRNA level in human chronic myelogenous leukemia.
abstract: Bcr/abl fusion gene is the marker gene in chronic myelogenous leukemia (CML) and becomes the target for CML therapy. Although Imatinib opened a new way to treat CML, the resistance to the drug caused by bcr/abl fusion protein mutation stimulated search for new molecules to inhibit bcr/abl expression. In our research, it was found that a novel 2-aminosteroid (H89465) possessed special mechanism in treating CML. H89465 inhibits the proliferation of both non-resistant and resistant CML cells such as K562, Meg-01 and clinical primary CML cells. It prolongs the survival time of NOD/SCID mice inoculated with K562 leukemia cells. The mechanism underlying the effects is concerned with down-regulation of bcr/abl mRNA expression followed by decreasing the BCR/ABL protein expression and tyrosine kinase activity in CML cells. Our results demonstrate that H89465 possesses the therapeutic potential in treating human CML.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. hequn888@yahoo.com
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.forename: Huanying
authors.initials: H
authors.lastname: Zhen
authors.forename: Yalin
authors.initials: Y
authors.lastname: Ying
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Birong
authors.initials: B
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: C561367:H89465; D012333:RNA, Messenger; D013256:Steroids; D016044:Fusion Proteins, bcr-abl