title: Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1.
abstract: We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be used for the treatment of patients with SNX2-ABL1+ ALL.
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan; Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Tomita
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan; Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan; Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Division of Pediatric Oncology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Osumi
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.affiliation: Department of Pediatrics, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Pediatric Oncology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Pediatrics, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan. Electronic address: kiyokawa-n@ncchd.go.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D000069439:Dasatinib; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D005822:Genetic Vectors; D006801:Humans; D000068877:Imatinib Mesylate; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000494:pharmacology; D012190:Retroviridae / Q000235:genetics; D058305:Sorting Nexins / Q000235:genetics* / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology; D014162:Transfection
chemical_list: C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D007377:Interleukin-3; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C505836:SNX2 protein, mouse; D058305:Sorting Nexins; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib
keywords: Acute lymphoblastic leukemia; BCR-ABL1; Phosphorylation; SNX2-ABL1; Tyrosine kinase inhibitor