慢性粒细胞白血病(CML)的里程碑历史和典型遗传学发现

Zhangyi Wu
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摘要

根据国际上每年1-2例/10万的估计发病率,美国国家罕见病组织将慢性粒细胞白血病(CML)归类为一种血液系统恶性罕见病。CML发生在所有年龄段,但常见于45-55岁组。雄性受影响略大于雌性。慢性粒细胞白血病是已知最古老的新面孔疾病之一,也是发展最快的疾病之一,在人类战胜该疾病的历史上有许多非凡的发现。CML在白血病和癌症研究甚至人类医学史上至少有九项首次发现:1845年首次被命名为白血病,1846年诊断为CML患者的第一例活病例,1865年首次在CML治疗中使用砷,1951年首次被定义为骨髓增生性疾病,1960年首次发现费城染色体(Ph染色体),1973年首次发现9号和22号染色体易位,1977年首次确定为来源于多能干骨造血干细胞阶段的克隆性血液恶性肿瘤,1984年首次发现染色体融合基因BCR-ABL作为致癌基因,1998年首次设计使用酪氨酸激酶抑制剂(TKI)的靶向治疗。慢性粒细胞白血病研究的足迹奠定了里程碑式的历史。在人类疾病的奥秘、Ph染色体的多向易位和最新的问题上,人们做出了引人注目和引人入胜的遗传学发现。本章将对慢性粒细胞白血病和慢性淋巴细胞白血病的结合进行综述,目的是从实验室到临床床边进一步加深对CML的理解。
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Milestone Histories and Paradigmatic Genetic Discoveries of Chronic Myeloid Leukemia (CML)
Chronic myeloid leukemia (CML) is classified as a hematological malignant rare disease by National Organization for Rare Disease (NORD, USA) based on the esti-mated incidence of 1–2 cases/100,000 per year internationally. CML occurs in all ages but commonly seen in the 45–55 years group. Males are slightly more affected than females. CML is one of the oldest known diseases with new faces and one of the fastest developing diseases with many extraordinary discoveries in human history of conquering the disease. CML possesses at least Nine First findings in leukemia and cancer research and even in human medical histories: the First named as leukemia in 1845, the First of a live case of CML patient diagnosed in 1846, the First used of arsenic in CML treatment in 1865, the First defined as a myeloproliferative disorder in 1951, the First finding of Philadelphia chromosome (Ph chromosome) in 1960, the First finding of chromosome 9 and 22 translocations in 1973, the First identified as a clonal hematological malignancy derived from the stage of pluripotent bone hematopoietic stem cells in 1977, the First finding of the chromosomal fusion gene-BCR-ABL as an oncogene in 1984, and the First designed target therapy of use of tyrosine kinase inhibitor (TKI) in 1998. The footprints of the studies on CML established the milestone histories. Remarkable and fascinating genetic discoveries were made of the mysteries of human diseases, the multiway translocation of Ph chromosome, and the latest issues. The association of the combination of chronic myeloid leukemia and chronic lymphocytic leukemia will be reviewed in this chapter with the aim of increasing the understanding of CML further from laboratory bench to clinical bedside.
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