The Philadelphia chromosome in leukemogenesis

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英文篇名：The Philadelphia chromosome in leukemogenesis 作者：Zhi?Jie ; Kang ; Yu?Fei ; Liu ; Ling?Zhi ; Xu ; Zi?Jie ; Long ; Dan ; Huang ; Ya ; Yang ; Bing ; Liu ; Jiu?Xing ; Feng ; Yu?Jia ; Pan ; Jin?Song ; Yan ; Quentin ; Liu 英文作者：Zhi?Jie Kang;Yu?Fei Liu;Ling?Zhi Xu;Zi?Jie Long;Dan Huang;Ya Yang;Bing Liu;Jiu?Xing Feng;Yu?Jia Pan;Jin?Song Yan;Quentin Liu;Department of Hematology,The Second Affiliated Hospital,Institute of Cancer Stem Cell,Dalian Medical University;State Key Laboratory of Oncology in South China,Sun Yat?sen University Cancer Center;Department of Oncology,The Second Affiliated Hospital,Dalian Medical University;Department of Hematology,The Third Affiliated Hospital,Sun Yat?sen University; 英文关键词：Chronic myeloid leukemia;;BCR?ABL1;;Philadelphia chromosome;;Translocations;;Signaling pathway 中文刊名：AIZH 英文刊名：癌症(英文版) 机构：Department of Hematology,The Second Affiliated Hospital,Institute of Cancer Stem Cell,Dalian Medical University;State Key Laboratory of Oncology in South China,Sun Yat?sen University Cancer Center;Department of Oncology,The Second Affiliated Hospital,Dalian Medical University;Department of Hematology,The Third Affiliated Hospital,Sun Yat?sen University; 出版日期：2016-06-15 出版单位：Chinese Journal of Cancer 年：2016 期：v.35;No.299 基金：supported by the China Central Budget Recruitment Program of High?Level Overseas Talent (GDW 201221022066 to Q.Liu);; the National Basic Research Program of China (973 Program:No.2012CB967000 to Q.Liu);; the National Natural Science Foundation of China (NNSF No.81130040 to Q.Liu and No.81201686 to J.Xu);; the Program for Changjiang Scholars and Innovative Research Team in Universities (ITR 13049 to Q.Liu);; the Liaoning (NSF 2014029102 to Q.Liu) 语种：英文; 页：AIZH201606002 页数：15 CN：06 ISSN：44-1195/R 分类号：5-19

摘要

The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Phila?delphia chromosome(Ph) and is a hallmark of chronic myeloid leukemia(CML).In leukemia cells,Ph not only impairs the physiological signaling pathways but also disrupts genomic stability.This aberrant fusion gene encodes the breakpoint cluster region?proto?oncogene tyrosine?protein kinase(BCR?ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity.The kinase activity is responsible for maintaining proliferation,inhibiting differentia?tion,and conferring resistance to cell death.During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase,the expression patterns of different BCR?ABL1 transcripts vary.Each BCR?ABL1 transcript is present in a distinct leukemia phenotype,which predicts both response to therapy and clinical outcome.Besides CML,the Ph is found in acute lymphoblastic leukemia,acute myeloid leukemia,and mixed?phenotype acute leukemia.Here,we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph?positive leukemia and highlight key findings regarding leukemogenesis.
        The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Phila?delphia chromosome(Ph) and is a hallmark of chronic myeloid leukemia(CML).In leukemia cells,Ph not only impairs the physiological signaling pathways but also disrupts genomic stability.This aberrant fusion gene encodes the breakpoint cluster region?proto?oncogene tyrosine?protein kinase(BCR?ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity.The kinase activity is responsible for maintaining proliferation,inhibiting differentia?tion,and conferring resistance to cell death.During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase,the expression patterns of different BCR?ABL1 transcripts vary.Each BCR?ABL1 transcript is present in a distinct leukemia phenotype,which predicts both response to therapy and clinical outcome.Besides CML,the Ph is found in acute lymphoblastic leukemia,acute myeloid leukemia,and mixed?phenotype acute leukemia.Here,we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph?positive leukemia and highlight key findings regarding leukemogenesis.

引文

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