title: The short isoform of the long-type PML-RARA fusion gene in acute promyelocytic leukaemia lacks sensitivity to all-trans-retinoic acid.
abstract: Alternative splicing is associated with human disease. In acute promyelocytic leukaemia (APL) patients with the long (L)-type promyelocytic leukaemia-retinoic acid receptor α fusion gene (PML-RARA), three alternative splicing isoforms can be detected: E5(+)E6(+), E5(-)E6(+), and E5(-)E6(-). This study is the first to demonstrate that alternative splicing of L-type PML-RARA is associated with time to achieve complete remission (CR) in APL. Higher expression of the E5(-)E6(-) isoform, the short isoform, was related to longer time to achieve CR. Each isoform was constructed into recombinant lentiviral vector and transfected into U937 cells. Compared with the E5(-)E6(+) and E5(+)E6(+) groups, the U937 cells with E5(-)E6(-) showed lower sensitivity to all-trans-retinoic acid treatment.
authors.affiliation: Department of Hematology, Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tan
authors.forename: Sicheng
authors.initials: S
authors.lastname: Bian
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xu
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Chen
authors.forename: Xiling
authors.initials: X
authors.lastname: Qi
authors.forename: Fanggang
authors.initials: F
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Haixiu
authors.initials: H
authors.lastname: Guo
authors.forename: Aining
authors.initials: A
authors.lastname: Xu
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
mesh_terms: D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D023061:Gene Order; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D059368:RNA Isoforms; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D059368:RNA Isoforms; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin