ABL1基因所编码的蛋白存在于细胞核与细胞质中,属于酪氨酸激酶,主要参与细胞的分化、分裂与应激反应等,ABL1蛋白的SH3结构域对该蛋白起着负调控作用,SH3结构域的缺失会使ABL1成为原癌基因,ABL1蛋白将持续激活导致细胞发生癌变。在肿瘤细胞中发现ABL1基因与其它多种基因发生融合,最常见的为t(9;22)染色体易位,导致BCR(breakpoint cluster region)与ABL1基因的融合,9号与22号染色体易位产生变异的染色体也叫费城染色体( Philadelphia chromosome,Ph),这种类型的融合基因常见于慢性髓细胞白血病。

基因名:ABL1
别名:ABL,JTK7,bcr/abl,c-ABL,c-ABL1,p150,v-abl
基因ID:25
Chromosome:
(GRCh37)
9 Start: 133589333 End: 133763062 Strand: 1
药物: 阿昔替尼  博舒替尼  达沙替尼  伊马替尼  Imatinib Mesilate Imatinib Mesylate Imatinib (STI571) 尼洛替尼,尼罗替尼  高三尖杉酯碱  帕纳替尼/普纳替尼/波纳替尼  Tyrosine Kinase Inhibitor 
ABL1 基因突变与药物
ABL1 基因突变 BCR-ABL T315I
Allele Registry ID:CA122575别名:THR334ILE,RS121913459,BCR-ABL THR315ILE
ClinVar ID:12624

虽然伊马替尼的疗效已经彻底改变了慢性粒细胞白血病(CML)的治疗,但它仍然不是一个治愈所有。在CML患者的一小部分患者中,既有最初的耐药性,也有因选择而获得的耐药性。ABL激酶域突变t315i(又名t334i)是一种对伊马替尼产生耐药性的突变。针对BCR-ABL的第二代TKI(达沙替尼和波那替尼)已显示出治疗耐药病例的疗效。
While the efficacy of imatinib has revolutionized chronic myelogenous leukemia (CML) treatment, it is still not a cure-all. Both initial resistance and acquired resistance as a result of selection have been seen in a small subset of CML patients. The ABL kinase domain mutation T315I (aka T334I) has been shown to be one such mutation that confers resistance to imatinib. Second generation TKI's (dasatinib and ponatinib) specific to BCR-ABL have shown efficacy in treating resistant cases.

基因突变位点
Ref. Build: GRCh37   Ensembl Version: 75
Chr.StartStopRef. sVar. Bases
9133748283133748283CT
Transcript
ENST00000318560.5
基因序列
NM_007313.2:c.1001C>003eT
NP_005148.2:p.Thr315Ile
ENST00000372348.2:c.1001C>003eT
NC_000009.11:g.133748283C>003eT