title: RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations.
abstract: Recently, RCSD1 was identified as a novel gene fusion partner of the ABL1 gene. The RCSD1 gene, located at 1q23, is involved in t(1;9)(q23;q34) translocation in acute B lymphoblastic leukemia. Here we describe RCSD1-ABL1-positive B-cell acute lymphoblastic leukemia (ALL) followed by rapid clonal evolution exhibiting three rare reciprocal translocations. We performed breakpoint analysis of the transcript expressed by the RCSD1-ABL1 fusion gene. RT-PCR and sequence analyses detected transcription of a single RCSD1-ABL1 fusion gene variant, which had breakpoints in exon 3 of RCSD1 and exon 4 of ABL1. The RCSD1 portion of the RCSD1-ABL1 fusion transcript consists of exons 1, 2, and 3. Tyrosine kinase inhibitors, imatinib and dasatinib, coadministered with dexamethasone achieved transient clinical effects in the present RCSD1-ABL1-positive ALL. However, leukemic cells rapidly became refractory to this treatment following the subsequent development of three additional reciprocal chromosomal translocations, t(5;16)(q33;q24), dic(18;20)(p11.2;q11.2) and t(10;19)(q24;p13.3). The present RCSD1-ABL1-positive ALL may represent a state of high chromosomal instability.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. inokuchi@nms.ac.jp.
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakita
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Hirakawa
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Tamai
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yokose
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Dan
mesh_terms: D059786:Abnormal Karyotype; D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D003907:Dexamethasone / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005091:Exons; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C506059:RCSD1 protein, human; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl