Title:
LEUKEMIA STEM CELL MARKERS
Document Type and Number:
WIPO Patent Application WO2010110346
Kind Code:
A1
Abstract:
Provided are a therapeutic means and so on for completely curing acute myeloid leukemia (AML), which are established by finding molecular targets specific to human leukemic stem cells (LSCs). A test method for estimating the first onset or recurrence of AML which comprises: (1) a step for measuring the expression levels of LSC marker genes in a biological sample collected from a test subject with the use of the transcription products or translation products of said genes as the subjects; and (2) a step for comparing the expression levels, obtained in the measurement step, to standards, wherein said LSC marker genes consist of 2 to 218 genes. A therapeutic agent for AML targeting LSC comprising, as the active ingredient, a substance which is capable of inhibiting the expression of a gene selected from the LSC marker genes, or a substance which is capable of inhibiting the activity of the translation product of said gene. A method for producing a sample containing hematopoietic cells for autogenous or allogenic transplantation into an AML patient, which comprises a step for obtaining an LSC-purged sample using at least one kind of LSC marker as an indicator. The aforesaid LSC marker genes are as defined in the description.
Inventors:
ISHIKAWA FUMIHIKO (JP)
OHARA OSAMU (JP)
SAITO YORIKO (JP)
KITAMURA HIROSHI (JP)
HIJIKATA ATSUSHI (JP)
OZAWA HIDETOSHI (JP)
SHULTZ LEONARD D (US)
OHARA OSAMU (JP)
SAITO YORIKO (JP)
KITAMURA HIROSHI (JP)
HIJIKATA ATSUSHI (JP)
OZAWA HIDETOSHI (JP)
SHULTZ LEONARD D (US)
Application Number:
PCT/JP2010/055131
Publication Date:
September 30, 2010
Filing Date:
March 24, 2010
Export Citation:
Assignee:
RIKEN (JP)
ISHIKAWA FUMIHIKO (JP)
OHARA OSAMU (JP)
SAITO YORIKO (JP)
KITAMURA HIROSHI (JP)
HIJIKATA ATSUSHI (JP)
OZAWA HIDETOSHI (JP)
SHULTZ LEONARD D (US)
ISHIKAWA FUMIHIKO (JP)
OHARA OSAMU (JP)
SAITO YORIKO (JP)
KITAMURA HIROSHI (JP)
HIJIKATA ATSUSHI (JP)
OZAWA HIDETOSHI (JP)
SHULTZ LEONARD D (US)
International Classes:
C12Q1/68; A61K35/28; C12N15/09
Domestic Patent References:
| WO2009051238A1 | 2009-04-23 | |||
| WO2005045434A2 | 2005-05-19 | |||
| WO1994025585A1 | 1994-11-10 |
Foreign References:
| JP2007527238A | 2007-09-27 | |||
| JP2008068892A | 2008-03-27 | |||
| JPH0373280B2 | 1991-11-21 | |||
| JPH04506458A | 1992-11-12 | |||
| JPS62296890A | 1987-12-24 | |||
| JPH04504365A | 1992-08-06 | |||
| JPH06500233A | 1994-01-13 |
Other References:
NAOKI HOSEN ET AL.: "CD96 wa Hakketsubyo Kansaibo Tokuiteki Saibo Hyomen Marker de aru", JAPANESE JOURNAL OF CLINICAL IMMUNOLOGY, vol. 30, no. 4, 2007, pages 349, XP008154603
NAOKI HOSEN ET AL.: "CD96 wa Hito Kyusei Kotsuzuisei Hakketsubyo ni Oite Hakketsubyo Kansaibo to Seijo Zoketsu Kaisaibo o Kubetsu suru Marker de aru", DAI 66 KAI PROCEEDINGS OF THE JAPANESE CANCER ASSOCIATION, 20 August 2007 (2007-08-20), pages 76 - 77, XP008163576
HOSEN, N. ET AL.: "CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia", PROC. NATL. ACAD. SCI. U.S.A., vol. 104, no. 26, 2007, pages 11008 - 11013, XP008109009
STIREWALT, D., L.. ET AL.: "Identification of Genes with Abnormal Expression Changes in Acute Myeloid Leukemia", GENES, CHROMOSOMES AND CANCER, vol. 47, 2008, pages 8 - 20, XP055015530
KEIKI KUMANO ET AL.: "Zoketsuki Shuyo ni Okeru Gan Kansaibo Kenkyu no Shinten: AML Kansaibo Kenkyu no Shinten", HEMATOLOGY & ONCOLOGY, vol. 56, no. 6, 28 June 2008 (2008-06-28), pages 694 - 700, XP008154677
DORN, D., C. ET AL.: "The effect of cantharidins on leukemic stem cells", INT. J. CANCER, vol. 124, 19 November 2008 (2008-11-19), pages 2186 - 2199, XP008154594
PASSEGUE, E., JAMIESON, C.H., AILLES,L.E., WEISSMAN, I.L.: "Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?", PROC NATL ACAD SCI U S A, vol. 100, no. 1, 2003, pages 11842 - 11849
HOPE, K.J., JIN, L., DICK, J.E.: "Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity.", NAT IMMUNOL, vol. 5, 2004, pages 738 - 743, XP008109008, DOI: doi:10.1038/ni1080
JORDAN, C.T., GUZMAN, M.L.: "Mechanisms controlling pathogenesis and survival of leukemic stem cells.", ONCOGENE, vol. 23, 2004, pages 7178 - 7187
LAPIDOT, T. ET AL.: "A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.", NATURE, vol. 367, 1994, pages 645 - 648, XP003025767, DOI: doi:10.1038/367645a0
ISHIKAWA, F. ET AL.: "Chemotherapy-resistant human AML stem cells home to and engraft within the bone marrow endosteal region.", NATURE BIOTECHNOL, vol. 25, 2007, pages 1315 - 1321, XP002696540, DOI: doi:10.1038/NBT1350
CLARKE, M.F. ET AL.: "Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells.", CANCER RES, vol. 66, 2006, pages 9339 - 9344, XP002661633, DOI: doi:10.1158/0008-5472.CAN-06-3126
ISHIKAWA F. ET AL., NATURE BIOTECHNOL, vol. 25, 2007, pages 1315 - 1321
AUSUBEL ET AL.: "Current Protocols of Molecular Biology", 1997, JOHN WILEY AND SONS
PARKER, BARNES, METHODS IN MOLECULAR BIOLOGY, vol. 106, 1999, pages 247 - 283
HOD, BIOTECHNIQUES, vol. 13, 1992, pages 852 - 854
WEIS ET AL., TRENDS IN GENETICS, vol. 8, 1992, pages 263 - 264
HELD ET AL., GENOME RESEARCH, vol. 6, 1996, pages 986 - 994
SPROAT ET AL., NUCLE. ACID. RES., vol. 19, 1991, pages 733 - 738
COTTON ET AL., NUCL. ACID. RES., vol. 19, 1991, pages 2629 - 2635
ELLINGTON ET AL., NATURE, vol. 346, 1990, pages 818 - 822
TUERK ET AL., SCIENCE, vol. 249, 1990, pages 505 - 510
JIKKEN IGAKU, vol. 6, no. 10, 1988
NATURE GENETICS, vol. 15, 1997, pages 146 - 156
NATURE GENETICS, vol. 7, 1994, pages 13 - 21
NATURE, vol. 368, 1994, pages 856 - 859
S.E. HAYNESWORTH ET AL., BONE, vol. 13, 1992, pages 81
ZHIJIN ET AL., J. AM. STAT. ASSOC., vol. 99, 2004, pages 909 - 917
HONG ET AL., BIOINFORMATICS, vol. 22, 2006, pages 2825 - 2827
METHODS, vol. 25, 2001, pages 386 - 401
SHULTZ, L.D. ET AL.: "Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.", J IMMUNOL, vol. 154, 1995, pages 180 - 191
NATURE BIOTECHNOLOGY, 2007
BIOINFORMATICS, vol. 22, 2006, pages 2825
PROT NATL ACAD SCI USA, vol. 97, 2000, pages 1725
J EXP MED, vol. 191, 2000, pages 669
NAT CELL BIOL, vol. 3, 2001, pages 679
J BIOL CHEM, vol. 279, 2004, pages 1415
LEUKEMIA, vol. 19, 2005, pages 176
AM J PATHOL, vol. 161, 2002, pages 1657
GENES CHROMOSOMES CANCER, vol. 47, 2008, pages 8 - 20
BLOOD, vol. 110, 2007, pages 2659 - 2666
See also references of EP 2412825A4
NAOKI HOSEN ET AL.: "CD96 wa Hito Kyusei Kotsuzuisei Hakketsubyo ni Oite Hakketsubyo Kansaibo to Seijo Zoketsu Kaisaibo o Kubetsu suru Marker de aru", DAI 66 KAI PROCEEDINGS OF THE JAPANESE CANCER ASSOCIATION, 20 August 2007 (2007-08-20), pages 76 - 77, XP008163576
HOSEN, N. ET AL.: "CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia", PROC. NATL. ACAD. SCI. U.S.A., vol. 104, no. 26, 2007, pages 11008 - 11013, XP008109009
STIREWALT, D., L.. ET AL.: "Identification of Genes with Abnormal Expression Changes in Acute Myeloid Leukemia", GENES, CHROMOSOMES AND CANCER, vol. 47, 2008, pages 8 - 20, XP055015530
KEIKI KUMANO ET AL.: "Zoketsuki Shuyo ni Okeru Gan Kansaibo Kenkyu no Shinten: AML Kansaibo Kenkyu no Shinten", HEMATOLOGY & ONCOLOGY, vol. 56, no. 6, 28 June 2008 (2008-06-28), pages 694 - 700, XP008154677
DORN, D., C. ET AL.: "The effect of cantharidins on leukemic stem cells", INT. J. CANCER, vol. 124, 19 November 2008 (2008-11-19), pages 2186 - 2199, XP008154594
PASSEGUE, E., JAMIESON, C.H., AILLES,L.E., WEISSMAN, I.L.: "Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?", PROC NATL ACAD SCI U S A, vol. 100, no. 1, 2003, pages 11842 - 11849
HOPE, K.J., JIN, L., DICK, J.E.: "Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity.", NAT IMMUNOL, vol. 5, 2004, pages 738 - 743, XP008109008, DOI: doi:10.1038/ni1080
JORDAN, C.T., GUZMAN, M.L.: "Mechanisms controlling pathogenesis and survival of leukemic stem cells.", ONCOGENE, vol. 23, 2004, pages 7178 - 7187
LAPIDOT, T. ET AL.: "A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.", NATURE, vol. 367, 1994, pages 645 - 648, XP003025767, DOI: doi:10.1038/367645a0
ISHIKAWA, F. ET AL.: "Chemotherapy-resistant human AML stem cells home to and engraft within the bone marrow endosteal region.", NATURE BIOTECHNOL, vol. 25, 2007, pages 1315 - 1321, XP002696540, DOI: doi:10.1038/NBT1350
CLARKE, M.F. ET AL.: "Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells.", CANCER RES, vol. 66, 2006, pages 9339 - 9344, XP002661633, DOI: doi:10.1158/0008-5472.CAN-06-3126
ISHIKAWA F. ET AL., NATURE BIOTECHNOL, vol. 25, 2007, pages 1315 - 1321
AUSUBEL ET AL.: "Current Protocols of Molecular Biology", 1997, JOHN WILEY AND SONS
PARKER, BARNES, METHODS IN MOLECULAR BIOLOGY, vol. 106, 1999, pages 247 - 283
HOD, BIOTECHNIQUES, vol. 13, 1992, pages 852 - 854
WEIS ET AL., TRENDS IN GENETICS, vol. 8, 1992, pages 263 - 264
HELD ET AL., GENOME RESEARCH, vol. 6, 1996, pages 986 - 994
SPROAT ET AL., NUCLE. ACID. RES., vol. 19, 1991, pages 733 - 738
COTTON ET AL., NUCL. ACID. RES., vol. 19, 1991, pages 2629 - 2635
ELLINGTON ET AL., NATURE, vol. 346, 1990, pages 818 - 822
TUERK ET AL., SCIENCE, vol. 249, 1990, pages 505 - 510
JIKKEN IGAKU, vol. 6, no. 10, 1988
NATURE GENETICS, vol. 15, 1997, pages 146 - 156
NATURE GENETICS, vol. 7, 1994, pages 13 - 21
NATURE, vol. 368, 1994, pages 856 - 859
S.E. HAYNESWORTH ET AL., BONE, vol. 13, 1992, pages 81
ZHIJIN ET AL., J. AM. STAT. ASSOC., vol. 99, 2004, pages 909 - 917
HONG ET AL., BIOINFORMATICS, vol. 22, 2006, pages 2825 - 2827
METHODS, vol. 25, 2001, pages 386 - 401
SHULTZ, L.D. ET AL.: "Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.", J IMMUNOL, vol. 154, 1995, pages 180 - 191
NATURE BIOTECHNOLOGY, 2007
BIOINFORMATICS, vol. 22, 2006, pages 2825
PROT NATL ACAD SCI USA, vol. 97, 2000, pages 1725
J EXP MED, vol. 191, 2000, pages 669
NAT CELL BIOL, vol. 3, 2001, pages 679
J BIOL CHEM, vol. 279, 2004, pages 1415
LEUKEMIA, vol. 19, 2005, pages 176
AM J PATHOL, vol. 161, 2002, pages 1657
GENES CHROMOSOMES CANCER, vol. 47, 2008, pages 8 - 20
BLOOD, vol. 110, 2007, pages 2659 - 2666
See also references of EP 2412825A4
Attorney, Agent or Firm:
TAKASHIMA, HAJIME (JP)
Takashima 1 (JP)
Takashima 1 (JP)
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