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公开(公告)号：US07217568B2
公开(公告)日：2007-05-15
申请号：US10449795
申请日：2003-05-30
CPC分类号： C12Q1/6897 , C12N5/0647 , C12Q1/6881 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156
摘要： Methods and compositions are provided for the identification of stem cells and cancer stem cells. β-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at β-catenin, or members of the β-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized β-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.
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公开(公告)号：US07622255B2
公开(公告)日：2009-11-24
申请号：US11799817
申请日：2007-05-02
CPC分类号： C12Q1/6897 , C12N5/0647 , C12Q1/6881 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156
摘要： Methods and compositions are provided for the identification of stem cells and cancer stem cells. β-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at β-catenin, or members of the β-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized β-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.
摘要翻译： 提供了用于鉴定干细胞和癌症干细胞的方法和组合物。 β-连环蛋白也被鉴定为用于开发针对造血肿瘤，即白血病和淋巴瘤细胞的治疗部分的靶标，其可以包括针对β-连环蛋白的筛选测定或β-连环蛋白信号传导途径的成员。 造血细胞中的细胞增殖可以通过将稳定的β-连环蛋白引入造血细胞而改变，造血细胞在其经历凋亡的能力方面发生改变，但尚未完全转化。 永生化细胞可用于筛选测定，以及造血细胞经历转化的途径的分析。
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公开(公告)号：US07816088B2
公开(公告)日：2010-10-19
申请号：US10579540
申请日：2004-12-06
CPC分类号： G01N33/57426 , C12N5/0695 , G01N33/5011 , G01N2333/70589 , G01N2333/70596 , G01N2333/715
摘要： Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the bcatenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.
摘要翻译： 提供了白血病干细胞的分离群体。 这些细胞可用于实验评价，也可用作谱系和细胞特异性产物的来源，也可用于发现影响它们的因子或分子。 白血病干细胞的检测可用于预测疾病进展，复发和耐药发展。 LSC的增殖可通过干扰bcatenin途径的活化来抑制。 通过差异分析血液样品以分配一个或多个造血干细胞或祖细胞亚群，为白血病和白血病的临床分期提供方法。
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公开(公告)号：US20110076683A1
公开(公告)日：2011-03-31
申请号：US12875025
申请日：2010-09-02
IPC分类号： C12Q1/68 , C12N5/095 , C12Q1/04 , G01N33/574 , C12Q1/02
CPC分类号： G01N33/57426 , C12N5/0695 , G01N33/5011 , G01N2333/70589 , G01N2333/70596 , G01N2333/715
摘要： Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the β-catenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.
摘要翻译： 提供了白血病干细胞的分离群体。 这些细胞可用于实验评价，也可用作谱系和细胞特异性产物的来源，也可用于发现影响它们的因子或分子。 白血病干细胞的检测可用于预测疾病进展，复发和耐药发展。 LSC的增殖可能通过干扰β-联蛋白途径的活化来抑制。 通过差异分析血液样品以分配一个或多个造血干细胞或祖细胞亚群，为白血病和白血病的临床分期提供方法。
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公开(公告)号：US07514229B2
公开(公告)日：2009-04-07
申请号：US11528890
申请日：2006-09-27
CPC分类号： C12Q1/6883 , C12Q2600/112 , C12Q2600/118 , C12Q2600/158 , G01N33/5091 , G01N33/5094 , G01N33/6893 , G01N2800/22
摘要： Methods, systems and kits are provided for the clinical staging of blood disorders including myelodysplastic syndrome, myeloproliferative diseases and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets. Additional functional, genetic, gene expression, proteomic or other molecular analyses of the hematopoietic stem and progenitor cells from the patients can also be employed in the staging methods of the invention.
摘要翻译： 提供方法，系统和试剂盒用于血液病症的临床分期，包括骨髓增生异常综合征，骨髓增生性疾病和白血病，通过血液样品的差异分析来分配一个或多个造血干细胞或祖细胞亚群。 在本发明的分期方法中也可以使用来自患者的造血干细胞和祖细胞的其他功能，遗传，基因表达，蛋白质组学或其他分子分析。
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公开(公告)号：US20100287631A1
公开(公告)日：2010-11-11
申请号：US12447884
申请日：2007-11-02
申请人： Catriona Helen M. Jamieson , Ifat Geron , Annelie Abrahamsson , Edward Kavalerchik , Irving L. Weissman , Jason Gotlib
发明人： Catriona Helen M. Jamieson , Ifat Geron , Annelie Abrahamsson , Edward Kavalerchik , Irving L. Weissman , Jason Gotlib
IPC分类号： C12Q1/48 , C12Q1/68 , G01N33/573 , A01K67/00
CPC分类号： C12N9/1294 , A01K67/0271 , A01K2227/105 , A01K2267/0331 , C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136
摘要： Cancer specific splicing events in the Wnt/β-catenin signaling pathway are associated with progression of myelogenous leukemia. Misspliced genes of interest include GSK3β. In some embodiments of the invention, polynucleotides are provided that correspond to misspliced GSK3β transcripts associated with cancer. Such transcripts are characterized by a deletion of exon (8), and particularly in exon (8) and (9). Detection of such transcripts in cells is indicative of the presence of leukemia, and particularly of the presence of leukemia stem cells. In other embodiments, polypeptides are provided that are encoded by misspliced GSK3β transcripts associated with cancer. Such polypeptides are useful as diagnostic markers for cancer, and as a target for screening of therapeutic agents. Animal models comprising a human LSC having a misspliced GSK3b transcript provide a useful model for leukemia, for drug/gene screening in the prevention and treatment of leukemia in humans, etc.
摘要翻译： Wnt / bgr-catenin信号通路中的癌细胞特异性剪接事件与骨髓性白血病的进展有关。 感兴趣的未知基因包括GSK3＆bgr。 在本发明的一些实施方案中，提供了与错过的GSK3和bgr相对应的多核苷酸; 与癌症相关的成绩单。 这些转录物的特征在于外显子（8）的缺失，特别是在外显子（8）和（9）中。 细胞中这些转录物的检测表明存在白血病，特别是存在白血病干细胞。 在其他实施方案中，提供了由错过的GSK3和bgr编码的多肽; 与癌症相关的成绩单。 这样的多肽可用作癌症的诊断标记物，以及用作筛选治疗剂的靶标。 包含具有错误的GSK3b转录物的人LSC的动物模型为白血病提供了有用的模型，用于预防和治疗人类白血病等的药物/基因筛选。
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公开(公告)号：US08153388B2
公开(公告)日：2012-04-10
申请号：US12875025
申请日：2010-09-02
CPC分类号： G01N33/57426 , C12N5/0695 , G01N33/5011 , G01N2333/70589 , G01N2333/70596 , G01N2333/715
摘要： Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the β-catenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.
摘要翻译： 提供了白血病干细胞的分离群体。 这些细胞可用于实验评价，也可用作谱系和细胞特异性产物的来源，也可用于发现影响它们的因子或分子。 白血病干细胞的检测可用于预测疾病进展，复发和耐药发展。 LSC的增殖可能通过干扰β-联蛋白途径的活化来抑制。 通过差异分析血液样品以分配一个或多个造血干细胞或祖细胞亚群，为白血病和白血病的临床分期提供方法。
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公开(公告)号：US20090191202A1
公开(公告)日：2009-07-30
申请号：US12321215
申请日：2009-01-15
IPC分类号： A61K39/395 , C12N5/08
CPC分类号： A61K38/1709 , A61K35/14 , C07K16/2896 , G01N33/5091 , G01N33/5094 , G01N33/566 , G01N33/574 , G01N2800/22
摘要： Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.
摘要翻译： 提供了用于操纵细胞吞噬作用的方法，包括造血细胞，例如， 循环造血细胞，骨髓细胞等; 和实体瘤细胞。 在本发明的一些实施方案中，循环细胞是造血干细胞或造血祖细胞，特别是在移植上下文中，其中希望保护免受吞噬作用。 在其他实施方案中，循环细胞是白血病细胞，特别是急性骨髓性白血病（AML），其中希望增加吞噬作用。
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公开(公告)号：US20080020407A1
公开(公告)日：2008-01-24
申请号：US10579540
申请日：2004-12-06
IPC分类号： G01N33/574 , C12N5/08
CPC分类号： G01N33/57426 , C12N5/0695 , G01N33/5011 , G01N2333/70589 , G01N2333/70596 , G01N2333/715
摘要： Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the beatenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.
摘要翻译： 提供了白血病干细胞的分离群体。 这些细胞可用于实验评价，也可用作谱系和细胞特异性产物的来源，也可用于发现影响它们的因子或分子。 白血病干细胞的检测可用于预测疾病进展，复发和耐药发展。 LSC的增殖可能通过干扰扑热息痛途径的活化来抑制。 通过差异分析血液样品以分配一个或多个造血干细胞或祖细胞亚群，为白血病和白血病的临床分期提供方法。
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公开(公告)号：US20110243853A1
公开(公告)日：2011-10-06
申请号：US12446203
申请日：2007-10-24
申请人： Catriona Helen M. Jamieson , Ken Kaushansky , Charlene Barroga , Ifat Geron , Annelie Schairer , Edward Kavalerchik
发明人： Catriona Helen M. Jamieson , Ken Kaushansky , Charlene Barroga , Ifat Geron , Annelie Schairer , Edward Kavalerchik
IPC分类号： A01K67/033 , A61K49/00 , C12Q1/02
CPC分类号： A01K67/0271 , A01K2207/15 , A01K2217/00 , A01K2227/105 , A01K2267/0381 , C12N9/1205 , G01N33/5088
摘要： Non human animal models are provided for diseases involving erythroid function, particularly myeloproliferative disease. The models are useful for testing and screening of biologically active agents that affect erythropoiesis, and erythroid function. In the animal models of the invention, a hematopoietic stem or progenitor cell (HSC) population that has been genetically altered by the introduction of a mutant JAK2 coding sequence is transplanted into an immunocompromised, xenogeneic, non-human recipient. The recipient animal is engrafted with the cell population at a high frequency, and develops a myeloproliferative disorder characterized by polycythemia.
摘要翻译： 非人类动物模型适用于涉及红系功能的疾病，特别是骨髓增生性疾病。 该模型对于影响红细胞生成和红细胞功能的生物活性剂的测试和筛选是有用的。 在本发明的动物模型中，通过引入突变体JAK2编码序列遗传改变的造血干细胞或祖细胞（HSC）群体被移植到免疫受损的异种非人受体中。 受体动物以高频率移植细胞群，并发展出以红细胞增多症为特征的骨髓增生性疾病。
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