The Philadelphia chromosome in leukemogenesis
10.1186/s40880-016-0108-0
- Author:
ZhiJieKang
1
;
YuFeiLiu
;
LingZhiXu
;
ZiJieLong
;
DanHuang
;
YaYang
;
BingLiu
;
JiuXingFeng
;
YuJiaPan
;
JinSongYan
;
QuentinLiu
Author Information
1. Department of Hematology
- Keywords:
Chronic myeloid leukemia;
BCR-ABL1;
Philadelphia chromosome;
Translocations;
Signaling pathway
- From:Chinese Journal of Cancer
2016;35(6):269-283
- CountryChina
- Language:Chinese
-
Abstract:
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 ifndings regarding leukemogenesis.
