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。

公开(公告)号：US20090263832A1

公开(公告)日：2009-10-22

申请号：US12086609

申请日：2006-11-29

申请人： Roberto Polakiewicz ,  Ting-Lei Gu ,  Valerie Goss ,  Kimberly Lee

发明人： Roberto Polakiewicz ,  Ting-Lei Gu ,  Valerie Goss ,  Kimberly Lee

IPC分类号： G01N33/573 ,  C12Q1/48 ,  C07K16/18 ,  C12N5/16 ,  C12N5/18

CPC分类号： G01N33/57426

摘要： The invention discloses nearly 123 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: protein kinases, adaptor/scaffold proteins, phosphatase/phospholipases, G proteins/GTPase activating proteins/guanine nucleotide exchange factors, cellular metabolism enzymes, DNA binding proteins, cytoskeletal proteins, cell cycle regulation proteins, proteases, RNA binding proteins, transcription proteins, translation initiation complex proteins, transferases, ubiquitin conjugating system proteins, vesicle proteins, actin binding proteins, apoptosis proteins, chemokine proteins, enzyme proteins extra cellular matrix proteins, helicases, hydrolases, immunoglobin superfamily proteins, inhibitor proteins, isomerases, ligases, lipid binding proteins, methyltransferases, motor proteins, receptor proteins, and chaperone proteins.

摘要翻译： 本发明公开了在信号转导蛋白中识别的近123个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白，如 以及使用试剂用于此目的的方法。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：蛋白激酶，衔接子/支架蛋白，磷酸酶/磷脂酶，G蛋白/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子，细胞代谢酶，DNA结合蛋白，细胞骨架蛋白，细胞 循环调节蛋白，蛋白酶，RNA结合蛋白，转录蛋白，翻译起始复合蛋白​​，转移酶，泛素缀合系统蛋白，囊泡蛋白，肌动蛋白结合蛋白，凋亡蛋白，趋化因子蛋白，酶蛋白超细胞基质蛋白，解旋酶，水解酶，免疫球蛋白 超家族蛋白，抑制蛋白，异构酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，受体蛋白和伴侣蛋白。