The Philadelphia chromosome in leukemogenesis

Cancer Communications

Ling-Zhi Xu¹  Zhi-Jie Kang¹  Bing Liu¹  Jiu-Xing Feng¹  Jin-Song Yan¹  Ya Yang²  Dan Huang³  Zi-Jie Long⁴  Yu-Fei Liu⁴  Yu-Jia Pan⁴  Quentin Liu⁴ 

[1]Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, P. R. China

[2]Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China

[3]Department of Oncology, The Second Affiliated Hospital, Dalian Medical University, Dalian, P. R. China

[4]State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

关键词: Chronic myeloid leukemia;    BCR-ABL1;    Philadelphia chromosome;    Translocations;    Signaling pathway;   

DOI  :  10.1186/s40880-016-0108-0

学科分类：肿瘤学

来源: Springer

【 摘 要 】

The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia 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 differentiation, 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.

【 授权许可】

CC BY