fbpx
维基百科

BCR基因

二月 08, 2023

BCR基因（英語：BCR gene），或称断裂点簇集区（英語：breakpoint cluster region），是bcr-abl融合基因的组成部分之一，其与费城染色体的形成机制有关。

Bcr-Abl肿瘤蛋白齐聚反应结构域
Bcr-Abl肿瘤蛋白齐聚反应结构域机制
鑑定
標誌Bcr-Abl_Oligo
PfamPF09036
InterPro（英语：InterPro）IPR015123
現有可用的蛋白結構：
Pfam結構 / ECOD
PDBRCSB PDB; PDBe; PDBj
PDBsum（英语：PDBsum）結構概要
Breakpoint cluster region
PDB rendering based on 1k1f.
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 BCR; ALL; BCR1; CML; D22S11; D22S662; PHL
扩展标识 遗传学：151410 鼠基因：88141 同源基因：3192 ChEMBL: 5146 GeneCards: BCR Gene
EC編號 2.7.11.1
直系同源体
物种 人类 小鼠
Entrez 613 110279
Ensembl ENSG00000186716 ENSMUSG00000009681
UniProt P11274 Q6PAJ1
mRNA序列 NM_004327 NM_001081412
蛋白序列 NP_004318 NP_001074881
基因位置 Chr 22:
23.52 – 23.66 Mb		 Chr 10:
75.06 – 75.18 Mb
PubMed查询 [1] [2]

病理学

一个22号染色体与9号染色体的相互易位作用而产生的费城染色体，它通常在慢性粒细胞性白血病患者体内发现。22号染色体的断裂点就在BCR基因中。这个易位作用产生了一种基于BCR基因和ABL基因进行编码而成的融合蛋白，其基因就位于9号染色体的断裂点上。尽管bcr-abl融合基因已经被广泛研究，但普通的BCR基因机制仍然不明。其蛋白产生一些丝氨酸或苏氨酸蛋白激酶活动，并是一类p21rac酶活化蛋白。[1]

Bcr-Abl肿瘤蛋白齐聚反应域（Bcr-Abl oncoprotein oligomerisation domain）位于BCR的氨基端（N-terminus），其为BCR-ABL融合蛋白的齐聚反应必不可少的基因之一。Bcr-Abl肿瘤蛋白齐聚反应域包含一个短状氨基端α螺旋（alpha-1），一个灵活的转角（Turn）和一个长状的C型α螺旋（alpha-2）。其螺旋体转角使得两个α螺旋能够保持平行定向。这一单体分子的蛋白质结构域，通过一个反平行的卷轴螺旋（coiled coil）形成为一个蛋白质二聚体（protein dimer）。其中两个α螺旋彼此之间发生了结构域对换，其中一个α-1螺旋氨基端进行交换，并挤压另个单体上的α-2螺旋（alpha-2）。两个蛋白质二聚体随后形成一个四聚体（tetramer）[2]。

相互机制

现今已经发现BCR基因与以下基因发生蛋白-蛋白交互作用（Protein-protein interaction）：PTPN6（英语：PTPN6）[3]、XPB（英语：XPB）[4]、猫肉瘤癌基因[5][6]、GRB10（英语：GRB10）[7]、CD117（英语：CD117）[8]、Grb2（英语：Grb2）[6][7][9][10][11][12]、MLLT4（英语：MLLT4）[13]、Abl基因（英语：ABL (gene)）[11][14][15]、HCK（英语：HCK）[16][17]、SOS1（英语：SOS1）[6][11]、PIK3CG（英语：PIK3CG）[7][18][19]、CRKL（英语：CRKL）[7][10][20][21]和桩蛋白[18][22]。

参考

  1. ^ Entrez Gene: BCR breakpoint cluster region. 
  2. ^ Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat. Struct. Biol. February 2002, 9 (2): 117–20. PMID 11780146. doi:10.1038/nsb747. 
  3. ^ Liedtke, M; Pandey P, Kumar S, Kharbanda S, Kufe D. Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase. Oncogene (ENGLAND). Oct 1998, 17 (15): 1889–92. ISSN 0950-9232. PMID 9788431. doi:10.1038/sj.onc.1202117. 
  4. ^ Takeda, N; Shibuya M, Maru Y. The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein. Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES). Jan 1999, 96 (1): 203–7. ISSN 0027-8424. PMC 15117  . PMID 9874796. doi:10.1073/pnas.96.1.203. 
  5. ^ Lionberger, J M; Smithgall T E. The c-Fes protein-tyrosine kinase suppresses cytokine-independent outgrowth of myeloid leukemia cells induced by Bcr-Abl. Cancer Res. (UNITED STATES). Feb 2000, 60 (4): 1097–103. ISSN 0008-5472. PMID 10706130. 
  6. ^ 6.0 6.1 6.2 Maru, Y; Peters K L, Afar D E, Shibuya M, Witte O N, Smithgall T E. Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS. Mol. Cell. Biol. (UNITED STATES). Feb 1995, 15 (2): 835–42. ISSN 0270-7306. PMC 231961  . PMID 7529874. 
  7. ^ 7.0 7.1 7.2 7.3 Bai, R Y; Jahn T, Schrem S, Munzert G, Weidner K M, Wang J Y, Duyster J. The SH2-containing adapter protein GRB10 interacts with BCR-ABL. Oncogene (ENGLAND). Aug 1998, 17 (8): 941–8. ISSN 0950-9232. PMID 9747873. doi:10.1038/sj.onc.1202024. 
  8. ^ Hallek, M; Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb H J, Druker B, Griffin J D, Emmerich B, Ullrich A. Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells. Br. J. Haematol. (ENGLAND). Jul 1996, 94 (1): 5–16. ISSN 0007-1048. PMID 8757502. doi:10.1046/j.1365-2141.1996.6102053.x. 
  9. ^ Million, R P; Van Etten R A. The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood (UNITED STATES). Jul 2000, 96 (2): 664–70. ISSN 0006-4971. PMID 10887132. 
  10. ^ 10.0 10.1 Million, Ryan P; Harakawa Nari, Roumiantsev Sergei, Varticovski Lyuba, Van Etten Richard A. A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase. Mol. Cell. Biol. (United States). Jun 2004, 24 (11): 4685–95. ISSN 0270-7306. PMC 416425  . PMID 15143164. doi:10.1128/MCB.24.11.4685-4695.2004. 
  11. ^ 11.0 11.1 11.2 Puil, L; Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci P G, Arlinghaus R, Pawson T. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J. (ENGLAND). Feb 1994, 13 (4): 764–73. ISSN 0261-4189. PMC 394874  . PMID 8112292. 
  12. ^ Ma, G; Lu D, Wu Y, Liu J, Arlinghaus R B. Bcr phosphorylated on tyrosine 177 binds Grb2. Oncogene (ENGLAND). May 1997, 14 (19): 2367–72. ISSN 0950-9232. PMID 9178913. doi:10.1038/sj.onc.1201053. 
  13. ^ Radziwill, G; Erdmann R A, Margelisch U, Moelling K. The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain. Mol. Cell. Biol. (United States). Jul 2003, 23 (13): 4663–72. ISSN 0270-7306. PMC 164848  . PMID 12808105. doi:10.1128/MCB.23.13.4663-4672.2003. 
  14. ^ Ling, Xiaoyang; Ma Guozhen, Sun Tong, Liu Jiaxin, Arlinghaus Ralph B. Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr. Cancer Res. (United States). Jan 2003, 63 (2): 298–303. ISSN 0008-5472. PMID 12543778. 
  15. ^ Pendergast, A M; Muller A J, Havlik M H, Maru Y, Witte O N. BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. Cell (UNITED STATES). Jul 1991, 66 (1): 161–71. ISSN 0092-8674. PMID 1712671. doi:10.1016/0092-8674(91)90148-R. 
  16. ^ Stanglmaier, M; Warmuth M, Kleinlein I, Reis S, Hallek M. The interaction of the Bcr-Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains. Leukemia (England). Feb 2003, 17 (2): 283–9. ISSN 0887-6924. PMID 12592324. doi:10.1038/sj.leu.2402778. 
  17. ^ Lionberger, J M; Wilson M B, Smithgall T E. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J. Biol. Chem. (UNITED STATES). Jun 2000, 275 (24): 18581–5. ISSN 0021-9258. PMID 10849448. doi:10.1074/jbc.C000126200. 
  18. ^ 18.0 18.1 Salgia, R; Sattler M, Pisick E, Li J L, Griffin J D. p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl. Exp. Hematol. (UNITED STATES). Feb 1996, 24 (2): 310–3. ISSN 0301-472X. PMID 8641358. 
  19. ^ Skorski, T; Kanakaraj P, Nieborowska-Skorska M, Ratajczak M Z, Wen S C, Zon G, Gewirtz A M, Perussia B, Calabretta B. Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. Blood (UNITED STATES). Jul 1995, 86 (2): 726–36. ISSN 0006-4971. PMID 7606002. 
  20. ^ Heaney, C; Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker B J. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood (UNITED STATES). Jan 1997, 89 (1): 297–306. ISSN 0006-4971. PMID 8978305. 
  21. ^ Kolibaba, K S; Bhat A, Heaney C, Oda T, Druker B J. CRKL binding to BCR-ABL and BCR-ABL transformation. Leuk. Lymphoma (SWITZERLAND). Mar 1999, 33 (1-2): 119–26. ISSN 1042-8194. PMID 10194128. doi:10.3109/10428199909093732. 
  22. ^ Salgia, R; Li J L, Lo S H, Brunkhorst B, Kansas G S, Sobhany E S, Sun Y, Pisick E, Hallek M, Ernst T. Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL. J. Biol. Chem. (UNITED STATES). Mar 1995, 270 (10): 5039–47. ISSN 0021-9258. PMID 7534286. doi:10.1074/jbc.270.10.5039. 

外部链接

延伸阅读

  • Wang L, Seale J, Woodcock BE, Clark RE. e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts.. Leukemia. 2002, 16 (8): 1562–3. PMID 12145699. doi:10.1038/sj.leu.2402600. 

二月 08, 2023
bcr基因, 英語, gene, 或称断裂点簇集区, 英語, breakpoint, cluster, region, 是bcr, abl融合基因的组成部分之一, 其与费城染色体的形成机制有关, abl肿瘤蛋白齐聚反应结构域bcr, abl肿瘤蛋白齐聚反应结构域机制鑑定標誌bcr, oligopfampf09036interpro, 英语, interpro, ipr015123現有可用的蛋白結構, pfam結構, ecodpdbrcsb, pdbe, pdbjpdbsum, 英语, pdbsum, 結構概要bre. BCR基因 英語 BCR gene 或称断裂点簇集区 英語 breakpoint cluster region 是bcr abl融合基因的组成部分之一 其与费城染色体的形成机制有关 Bcr Abl肿瘤蛋白齐聚反应结构域Bcr Abl肿瘤蛋白齐聚反应结构域机制鑑定標誌Bcr Abl OligoPfamPF09036InterPro 英语 InterPro IPR015123現有可用的蛋白結構 Pfam結構 ECODPDBRCSB PDB PDBe PDBjPDBsum 英语 PDBsum 結構概要Breakpoint cluster regionPDB rendering based on 1k1f 有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表1K1F 2AIN标识代号BCR ALL BCR1 CML D22S11 D22S662 PHL扩展标识遗传学 151410 鼠基因 88141 同源基因 3192 ChEMBL 5146 GeneCards BCR GeneEC編號2 7 11 1基因本体论描述分子功能 protein serine threonine kinase activity protein tyrosine kinase activity Rho guanyl nucleotide exchange factor activity GTPase activator activity protein binding ATP binding phospholipid binding kinase activity enzyme binding Rac GTPase activator activity细胞成分 cytosol plasma membrane生物过程 protein phosphorylation signal transduction small GTPase mediated signal transduction brain development actin cytoskeleton organization negative regulation of cell migration response to lipopolysaccharide inner ear morphogenesis negative regulation of neutrophil degranulation protein autophosphorylation platelet derived growth factor receptor signaling pathway negative regulation of inflammatory response positive regulation of phagocytosis neuromuscular process controlling balance regulation of small GTPase mediated signal transduction regulation of cell cycleSources Amigo QuickGO直系同源体物种人类小鼠Entrez613110279EnsemblENSG00000186716ENSMUSG00000009681UniProtP11274Q6PAJ1mRNA序列NM 004327NM 001081412蛋白序列NP 004318NP 001074881基因位置Chr 22 23 52 23 66 MbChr 10 75 06 75 18 MbPubMed查询 1 2 查论编 目录 1 病理学 2 相互机制 3 参考 4 外部链接 5 延伸阅读病理学 编辑一个22号染色体与9号染色体的相互易位作用而产生的费城染色体 它通常在慢性粒细胞性白血病患者体内发现 22号染色体的断裂点就在BCR基因中 这个易位作用产生了一种基于BCR基因和ABL基因进行编码而成的融合蛋白 其基因就位于9号染色体的断裂点上 尽管bcr abl融合基因已经被广泛研究 但普通的BCR基因机制仍然不明 其蛋白产生一些丝氨酸或苏氨酸蛋白激酶活动 并是一类p21rac酶活化蛋白 1 Bcr Abl肿瘤蛋白齐聚反应域 Bcr Abl oncoprotein oligomerisation domain 位于BCR的氨基端 N terminus 其为BCR ABL融合蛋白的齐聚反应必不可少的基因之一 Bcr Abl肿瘤蛋白齐聚反应域包含一个短状氨基端a螺旋 alpha 1 一个灵活的转角 Turn 和一个长状的C型a螺旋 alpha 2 其螺旋体转角使得两个a螺旋能够保持平行定向 这一单体分子的蛋白质结构域 通过一个反平行的卷轴螺旋 coiled coil 形成为一个蛋白质二聚体 protein dimer 其中两个a螺旋彼此之间发生了结构域对换 其中一个a 1螺旋氨基端进行交换 并挤压另个单体上的a 2螺旋 alpha 2 两个蛋白质二聚体随后形成一个四聚体 tetramer 2 相互机制 编辑现今已经发现BCR基因与以下基因发生蛋白 蛋白交互作用 Protein protein interaction PTPN6 英语 PTPN6 3 XPB 英语 XPB 4 猫肉瘤癌基因 5 6 GRB10 英语 GRB10 7 CD117 英语 CD117 8 Grb2 英语 Grb2 6 7 9 10 11 12 MLLT4 英语 MLLT4 13 Abl基因 英语 ABL gene 11 14 15 HCK 英语 HCK 16 17 SOS1 英语 SOS1 6 11 PIK3CG 英语 PIK3CG 7 18 19 CRKL 英语 CRKL 7 10 20 21 和桩蛋白 18 22 参考 编辑 Entrez Gene BCR breakpoint cluster region Zhao X Ghaffari S Lodish H Malashkevich VN Kim PS Structure of the Bcr Abl oncoprotein oligomerization domain Nat Struct Biol February 2002 9 2 117 20 PMID 11780146 doi 10 1038 nsb747 Liedtke M Pandey P Kumar S Kharbanda S Kufe D Regulation of Bcr Abl induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase Oncogene ENGLAND Oct 1998 17 15 1889 92 ISSN 0950 9232 PMID 9788431 doi 10 1038 sj onc 1202117 引文使用过时参数coauthors 帮助 Takeda N Shibuya M Maru Y The BCR ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein Proc Natl Acad Sci U S A UNITED STATES Jan 1999 96 1 203 7 ISSN 0027 8424 PMC 15117 PMID 9874796 doi 10 1073 pnas 96 1 203 引文使用过时参数coauthors 帮助 Lionberger J M Smithgall T E The c Fes protein tyrosine kinase suppresses cytokine independent outgrowth of myeloid leukemia cells induced by Bcr Abl Cancer Res UNITED STATES Feb 2000 60 4 1097 103 ISSN 0008 5472 PMID 10706130 引文使用过时参数coauthors 帮助 6 0 6 1 6 2 Maru Y Peters K L Afar D E Shibuya M Witte O N Smithgall T E Tyrosine phosphorylation of BCR by FPS FES protein tyrosine kinases induces association of BCR with GRB 2 SOS Mol Cell Biol UNITED STATES Feb 1995 15 2 835 42 ISSN 0270 7306 PMC 231961 PMID 7529874 引文使用过时参数coauthors 帮助 7 0 7 1 7 2 7 3 Bai R Y Jahn T Schrem S Munzert G Weidner K M Wang J Y Duyster J The SH2 containing adapter protein GRB10 interacts with BCR ABL Oncogene ENGLAND Aug 1998 17 8 941 8 ISSN 0950 9232 PMID 9747873 doi 10 1038 sj onc 1202024 引文使用过时参数coauthors 帮助 Hallek M Danhauser Riedl S Herbst R Warmuth M Winkler A Kolb H J Druker B Griffin J D Emmerich B Ullrich A Interaction of the receptor tyrosine kinase p145c kit with the p210bcr abl kinase in myeloid cells Br J Haematol ENGLAND Jul 1996 94 1 5 16 ISSN 0007 1048 PMID 8757502 doi 10 1046 j 1365 2141 1996 6102053 x 引文使用过时参数coauthors 帮助 Million R P Van Etten R A The Grb2 binding site is required for the induction of chronic myeloid leukemia like disease in mice by the Bcr Abl tyrosine kinase Blood UNITED STATES Jul 2000 96 2 664 70 ISSN 0006 4971 PMID 10887132 引文使用过时参数coauthors 帮助 10 0 10 1 Million Ryan P Harakawa Nari Roumiantsev Sergei Varticovski Lyuba Van Etten Richard A A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel Abl ETV6 Abl tyrosine kinase Mol Cell Biol United States Jun 2004 24 11 4685 95 ISSN 0270 7306 PMC 416425 PMID 15143164 doi 10 1128 MCB 24 11 4685 4695 2004 引文使用过时参数coauthors 帮助 11 0 11 1 11 2 Puil L Liu J Gish G Mbamalu G Bowtell D Pelicci P G Arlinghaus R Pawson T Bcr Abl oncoproteins bind directly to activators of the Ras signalling pathway EMBO J ENGLAND Feb 1994 13 4 764 73 ISSN 0261 4189 PMC 394874 PMID 8112292 引文使用过时参数coauthors 帮助 Ma G Lu D Wu Y Liu J Arlinghaus R B Bcr phosphorylated on tyrosine 177 binds Grb2 Oncogene ENGLAND May 1997 14 19 2367 72 ISSN 0950 9232 PMID 9178913 doi 10 1038 sj onc 1201053 引文使用过时参数coauthors 帮助 Radziwill G Erdmann R A Margelisch U Moelling K The Bcr kinase downregulates Ras signaling by phosphorylating AF 6 and binding to its PDZ domain Mol Cell Biol United States Jul 2003 23 13 4663 72 ISSN 0270 7306 PMC 164848 PMID 12808105 doi 10 1128 MCB 23 13 4663 4672 2003 引文使用过时参数coauthors 帮助 Ling Xiaoyang Ma Guozhen Sun Tong Liu Jiaxin Arlinghaus Ralph B Bcr and Abl interaction oncogenic activation of c Abl by sequestering Bcr Cancer Res United States Jan 2003 63 2 298 303 ISSN 0008 5472 PMID 12543778 引文使用过时参数coauthors 帮助 Pendergast A M Muller A J Havlik M H Maru Y Witte O N BCR sequences essential for transformation by the BCR ABL oncogene bind to the ABL SH2 regulatory domain in a non phosphotyrosine dependent manner Cell UNITED STATES Jul 1991 66 1 161 71 ISSN 0092 8674 PMID 1712671 doi 10 1016 0092 8674 91 90148 R 引文使用过时参数coauthors 帮助 Stanglmaier M Warmuth M Kleinlein I Reis S Hallek M The interaction of the Bcr Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains Leukemia England Feb 2003 17 2 283 9 ISSN 0887 6924 PMID 12592324 doi 10 1038 sj leu 2402778 引文使用过时参数coauthors 帮助 Lionberger J M Wilson M B Smithgall T E Transformation of myeloid leukemia cells to cytokine independence by Bcr Abl is suppressed by kinase defective Hck J Biol Chem UNITED STATES Jun 2000 275 24 18581 5 ISSN 0021 9258 PMID 10849448 doi 10 1074 jbc C000126200 引文使用过时参数coauthors 帮助 18 0 18 1 Salgia R Sattler M Pisick E Li J L Griffin J D p210BCR ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c Cbl Exp Hematol UNITED STATES Feb 1996 24 2 310 3 ISSN 0301 472X PMID 8641358 引文使用过时参数coauthors 帮助 Skorski T Kanakaraj P Nieborowska Skorska M Ratajczak M Z Wen S C Zon G Gewirtz A M Perussia B Calabretta B Phosphatidylinositol 3 kinase activity is regulated by BCR ABL and is required for the growth of Philadelphia chromosome positive cells Blood UNITED STATES Jul 1995 86 2 726 36 ISSN 0006 4971 PMID 7606002 引文使用过时参数coauthors 帮助 Heaney C Kolibaba K Bhat A Oda T Ohno S Fanning S Druker B J Direct binding of CRKL to BCR ABL is not required for BCR ABL transformation Blood UNITED STATES Jan 1997 89 1 297 306 ISSN 0006 4971 PMID 8978305 引文使用过时参数coauthors 帮助 Kolibaba K S Bhat A Heaney C Oda T Druker B J CRKL binding to BCR ABL and BCR ABL transformation Leuk Lymphoma SWITZERLAND Mar 1999 33 1 2 119 26 ISSN 1042 8194 PMID 10194128 doi 10 3109 10428199909093732 引文使用过时参数coauthors 帮助 Salgia R Li J L Lo S H Brunkhorst B Kansas G S Sobhany E S Sun Y Pisick E Hallek M Ernst T Molecular cloning of human paxillin a focal adhesion protein phosphorylated by P210BCR ABL J Biol Chem UNITED STATES Mar 1995 270 10 5039 47 ISSN 0021 9258 PMID 7534286 doi 10 1074 jbc 270 10 5039 引文使用过时参数coauthors 帮助 外部链接 编辑醫學主題詞表 MeSH BCR protein human延伸阅读 编辑Wang L Seale J Woodcock BE Clark RE e19a2 positive chronic myeloid leukaemia with BCR exon e16 deleted transcripts Leukemia 2002 16 8 1562 3 PMID 12145699 doi 10 1038 sj leu 2402600 取自 https zh wikipedia org w index php title BCR基因 amp oldid 59968699, 维基百科，wiki，书籍，书籍，图书馆，

文章

，阅读，下载，免费，免费下载，mp3，视频，mp4，3gp， jpg，jpeg，gif，png，图片，音乐，歌曲，电影，书籍，游戏，游戏。