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    MUTANT JAK3 KINASE IN HUMAN LEUKEMIA
    1.
    发明申请
    MUTANT JAK3 KINASE IN HUMAN LEUKEMIA 审中-公开
    MUTANT JAK3激活人类LEUKEMIA

    公开(公告)号：US20090285796A1

    公开(公告)日：2009-11-19

    申请号：US12161512

    申请日：2007-01-19

    申请人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

    发明人： Valerie Goss ,  Ting-lei Gu ,  Roberto Polakiewicz ,  Brian Druker ,  Denise Walters

    IPC分类号： A61K39/395 ,  C07H21/04 ,  C07K14/00 ,  C12N15/63 ,  C12N5/10 ,  C12N9/12 ,  C07K16/00 ,  C12Q1/68 ,  G01N33/53 ,  A61K31/7088 ,  A61P35/02

    CPC分类号： C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136

    摘要： In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

    摘要翻译： 根据本发明，已经在人类急性骨髓性白血病（AML）中发现JAK3激酶中的新的活化突变（丙氨酸572至缬氨酸）。 证实突变型JAK3激酶能够驱动急性巨核细胞白血病（AML-M7）的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变体JAK3激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测突变体多肽的试剂。 所公开的这种新的突变蛋白的鉴定并且使得能够确定生物样品中突变体JAK3激酶多肽的存在的新方法，用于筛选抑制突变蛋白质的化合物的方法，以及用于抑制突变体特征的癌症进展的方法 多核苷酸或多肽，其也由本发明提供。

    Translocation and mutant CSF1R Kinase in human leukemia
    2.
    发明申请
    Translocation and mutant CSF1R Kinase in human leukemia 审中-公开
    人类白血病易位和突变型CSF1R激酶

    公开(公告)号：US20090197269A1

    公开(公告)日：2009-08-06

    申请号：US12214616

    申请日：2008-06-20

    申请人： Ting-Lei Gu ,  Valerie Goss ,  Robert Polakiewicz ,  Brian Druker ,  Denise Walters

    发明人： Ting-Lei Gu ,  Valerie Goss ,  Robert Polakiewicz ,  Brian Druker ,  Denise Walters

    IPC分类号： C12Q1/68 ,  C12N15/11 ,  C12N15/00 ,  C12N15/87 ,  C12N5/06 ,  C12P21/00 ,  C12N9/96 ,  C07K16/18 ,  G01N33/574 ,  C12Q1/48

    CPC分类号： C12Q1/6886 ,  C07K14/47 ,  C07K14/7153 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q2600/106 ,  C12Q2600/136 ,  G01N2500/04

    摘要： In accordance with the invention, a novel gene translocation, (3p21, 5q33), in human myelogenous leukemia (AML) that results in a fusion protein combining part of RNA Binding Protein-6 (RBM6) with Macrophage Colony Stimulating Factor-1 Receptor (CSF1R) kinase has now been identified. The RBM6-CSF1R fusion protein and truncated CSF1R kinase itself, which both retain CSF1R tyrosine kinase activity, were confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant CSF1R kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein and truncated kinase enables new methods for determining the presence of these mutant CSF1R kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

    摘要翻译： 根据本发明，在人骨髓性白血病（AML）中的新型基因易位（3p21,5q33），其导致将部分RNA结合蛋白-6（RBM6）与巨噬细胞集落刺激因子-1受体（RBF6）结合的融合蛋白 CSF1R）激酶已被鉴定。 确认RBM6-CSF1R融合蛋白和截短的CSF1R激酶本身都保留了CSF1R酪氨酸激酶活性，以驱动急性巨核细胞白血病（AML-M7）的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变型CSF1R激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新的融合蛋白和截短的激酶的鉴定使得能够确定生物样品中这些突变型CSF1R激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于抑制癌症进展的方法 突变体多核苷酸或多肽，其也由本发明提供。

    Organic compounds
    3.
    发明申请
    Organic compounds 失效
    有机化合物

    公开(公告)号：US20070077640A1

    公开(公告)日：2007-04-05

    申请号：US11524626

    申请日：2006-09-20

    申请人： Brian Druker ,  Amie Corbin

    发明人： Brian Druker ,  Amie Corbin

    IPC分类号： C12N9/12 ,  C07H21/04 ,  C12P21/06

    CPC分类号： C12Q1/6886 ,  C07K14/82 ,  C12N9/12 ,  C12Q1/485 ,  C12Q2600/106 ,  G01N33/57426 ,  G01N2333/82

    摘要： The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

    摘要翻译： 本发明涉及分离的多肽，其包含由突变的功能性Ab1激酶结构域组成的氨基酸序列，所述突变的功能性激酶结构域对N- [4-甲基-3-（4-吡啶基） 吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺或其盐，用于筛选抑制酪氨酸激酶的化合物 这种多肽的活性，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及这种核酸分子在制备这些多肽中的用途，用于筛选抑制酪氨酸激酶的化合物 这些多肽的活性。

    DETECTION OF GLEEVEC RESISTANT MUTATIONS
    5.
    发明申请
    DETECTION OF GLEEVEC RESISTANT MUTATIONS 失效
    检测GLEEVEC抗性突变

    公开(公告)号：US20080090300A1

    公开(公告)日：2008-04-17

    申请号：US11873985

    申请日：2007-10-17

    申请人： Brian Druker ,  Amie Corbin

    发明人： Brian Druker ,  Amie Corbin

    IPC分类号： G01N33/68

    CPC分类号： C12Q1/6886 ,  C07K14/82 ,  C12N9/12 ,  C12Q1/485 ,  C12Q2600/106 ,  G01N33/57426 ,  G01N2333/82

    摘要： The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

    摘要翻译： 本发明涉及分离的多肽，其包含由突变的功能性Ab1激酶结构域组成的氨基酸序列，所述突变的功能性激酶结构域对N- [4-甲基-3-（4-吡啶基） 吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺或其盐，用于筛选抑制酪氨酸激酶的化合物 这种多肽的活性，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及这种核酸分子在制备这些多肽中的用途，用于筛选抑制酪氨酸激酶的化合物 这些多肽的活性。