Title:
IMANITIB-RESISTANT PHILADELPHIA CHROMOSOME-POSITIVE HUMAN ACUTE LYMPHOCYTIC LEUKEMIC CELL LINE AND UTILIZATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2004/094628
Kind Code:
A1
Abstract:
It is intended to provide a Philadelphia chromosome (Ph)-positive human acute lymphocytic leukemic cell line characterized by being resistant to imanitib mesylate at least at a concentration of 5 μM. In a preferred embodiment, the above-described chromosome contains a BCR/ABL fused gene and is characterized by having a point mutation which is a point mutation at the ATP-binding site of the gene product and comprises the substitution of threonine at the 315-position in the amino acid sequence of SEQ ID NO:2 by isoleucine. In a particularly preferred embodiment, a cell line TCC-Y/sr is provided. By screening a drug which inhibits the proliferation of the above imanitib mesylate-resistant cells, a remedy efficacious against imanitib mesylate-resistant human leukemia can be provided.
Inventors:
SATO YUKO (JP)
NAGAO HIROMASA (JP)
NAGAO HIROMASA (JP)
Application Number:
PCT/JP2003/013986
Publication Date:
November 04, 2004
Filing Date:
October 31, 2003
Export Citation:
Assignee:
SATO YUKO (JP)
NAGAO HIROMASA (JP)
NAGAO HIROMASA (JP)
International Classes:
C12N15/01; C12N5/09; C12N5/10; C12Q1/02; (IPC1-7): C12N5/08; C12Q1/00
Other References:
DATABASE BIOSIS [online] NGUYEN T K, ET AL: "STI571-RESISTANT PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA CELL LINE PRESENTING A SUBSTITUTE MUTATION OF THR315I1E", XP002974684, Database accession no. PREV200300367861
RICCI C, ET AL: "MUTATION IN THE ATP-BINDING POCKET OF THE ABL KINASE DOMAIN IN AN STI571-RESISTANT BCR/ABL-POSITIVE CELL LINE", CANCER RESEARCH, vol. 62, 2002, pages 5995 - 5998, XP002974685
KANO Y, ET AL: "IN VITRO CYTOTOXIC EFFECTS OF A TYROSINE KINASE INHIBITOR STI571 IN COMBINATION WITH COMMONLY USED ANTILEUKEMIC AGENTS", BLOOD, vol. 97, 2001, pages 1999 - 2007, XP001035243
GORRE E M, ET AL: "CLINICAL RESISTANCE TO STI-571 CANCER THERAPY CAUSED BY BCL-ABL GENE MUTATION OR AMPLIFICATION", SCIENCE, vol. 293, 2001, pages 876 - 880, XP001122032
RICCI C, ET AL: "MUTATION IN THE ATP-BINDING POCKET OF THE ABL KINASE DOMAIN IN AN STI571-RESISTANT BCR/ABL-POSITIVE CELL LINE", CANCER RESEARCH, vol. 62, 2002, pages 5995 - 5998, XP002974685
KANO Y, ET AL: "IN VITRO CYTOTOXIC EFFECTS OF A TYROSINE KINASE INHIBITOR STI571 IN COMBINATION WITH COMMONLY USED ANTILEUKEMIC AGENTS", BLOOD, vol. 97, 2001, pages 1999 - 2007, XP001035243
GORRE E M, ET AL: "CLINICAL RESISTANCE TO STI-571 CANCER THERAPY CAUSED BY BCL-ABL GENE MUTATION OR AMPLIFICATION", SCIENCE, vol. 293, 2001, pages 876 - 880, XP001122032
Attorney, Agent or Firm:
Kato, Asamichi (Bohsei Building 7th Floor, 20-12,
Shin-Yokohama 3-chome, Kohoku-k, Yokohama-shi Kanagawa, JP)
Download PDF: