title: Downregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13).
abstract: The translocation t(11;16)(q23;p13) has only been documented in patients with acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. We have established a myeloid cell line (SN-1) with the MLL-CBP fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1 cells were not induced to differentiate by all-trans retinoic acid (ATRA) and 1alpha,25-dihydroxyvitamin D(3) (VD3), retinoid X receptor (RXR) agonists, such as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the cells. Downregulation of the expression of the MLL-CBP fusion gene occurred during the differentiation of SN-1 cells. When SN-1 cells were treated with MLL-CBP antisense oligonucleotide, the cells were induced to differentiate by ATRA or VD3, suggesting that the MLL-CBP fusion gene dominant-negatively suppresses ATRA- or VD3-induced differentiation. Moreover, suboptimal concentrations of sodium butyrate, a histone deacetylase inhibitor, had a cooperative effect with ATRA or VD3 in inducing the differentiation of SN-1 cells. The downregulation of the expression of MLL-CBP mRNA was accompanied by the induction of differentiation. These findings suggest that RXR agonists or a clinically applicable combination of ATRA and butyrate derivatives might be useful for differentiation therapy in leukemia patients with the MLL-CBP fusion gene.
authors: Saitama Cancer Center Research Institute, Ina-machi, Saitama 362-0806, Japan.
authors: N
authors: N
authors: Niitsu
authors: Y
authors: Y
authors: Hayashi
authors: Y
authors: Y
authors: Honma
mesh_terms: D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D019677:Artificial Gene Fusion; D020148:Butyric Acid / Q000494:pharmacology; D050882:CREB-Binding Protein; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D002885:Chromosomes, Human, Pair 16; D004268:DNA-Binding Proteins / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011519:Proto-Oncogenes; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000819:agonists; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; C425552:Ro48 2250; D015534:Trans-Activators; D014157:Transcription Factors; D020148:Butyric Acid; D051788:Myeloid-Lymphoid Leukemia Protein; D000077556:Alitretinoin; D014212:Tretinoin; D011495:Histone-Lysine N-Methyltransferase; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D002117:Calcitriol