The Philadelphia chromosome in leukemogenesis.
The Philadelphia chromosome in leukemogenesis.
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费城染色体在白血病发生中的作用
DOI：
10.1186/s40880-016-0108-0
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发表时间：
2016-05-27
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
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作者：
Kang ZJ;Liu YF;Xu LZ;Long ZJ;Huang D;Yang Y;Liu B;Feng JX;Pan YJ;Yan JS;Liu Q
由相互易位t（9;22）（q34;q11）产生的截短的22号染色体被称为费城染色体（Ph），并且是慢性粒细胞白血病（CML）的标志。在白血病细胞中，Ph不仅损害生理信号通路，而且破坏基因组稳定性。该异常融合基因编码断裂点簇区原癌基因酪氨酸蛋白激酶（BCR-ABL 1）致癌蛋白，具有持续增强的酪氨酸激酶活性。激酶活性负责维持增殖、抑制分化并赋予细胞死亡抵抗力。在CML从慢性期到加速期再到急变期的进展过程中，不同BCR-ABL 1转录本的表达模式不同。每种BCR-ABL 1转录物都存在于不同的白血病表型中，可预测对治疗的反应和临床结果。除CML外，Ph还见于急性淋巴细胞白血病、急性髓细胞白血病和混合表型急性白血病。在这里，我们提供了一个概述的临床表现和细胞生物学的不同表型的Ph阳性白血病和突出的关键发现白血病。
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.