Chahardouli Bahram, Zaker Farhad, Mousavi Seied Asadollah, Kazemi Ahmad, Ostadali Mohammadreza, Nadali Fatemeh, Rostami Shahrbano, Alimoghaddam Kamran, Ghavamzade Ardeshir
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Shariati Hospital, Kargar Avenue, Tehran, Iran.
Hematology. 2013 May;18(3):158-62. doi: 10.1179/1607845412Y.0000000050. Epub 2013 Mar 27.
The occurrence of resistance mutations in the Abl kinase domain plays a central role in drug treatment failure in chronic myeloid leukemia (CML) patients. Among them, the T315I mutation at the gatekeeper position affects a common Abl kinase contact residue and confers complete resistance to all known ATP-competitive BCR-ABL inhibitors. In the present study, an allele-specific oligonucleotide reverse transcriptase polymerase chain reaction assay was used to detect T315I mutation in a cohort of 60 imatinib-resistant CML patients. In terms of disease phase, 43 patients (71%) were in late chronic phase, 4 (7%) in accelerated phase, and 13 (22%) in blastic phase. The prevalence of the T315I mutation was found to be 7% (4/60). All four patients with mutation were in advance phases and had previously lost all their responses. The results of the study confirmed that this method is low cost and easy tool to operate for T315I mutation screening and direct sequencing should be performed in positive cases for confirmation.
Abl激酶结构域中耐药性突变的发生在慢性粒细胞白血病（CML）患者的药物治疗失败中起着核心作用。其中，守门人位置的T315I突变影响一个常见的Abl激酶接触残基，并赋予对所有已知ATP竞争性BCR-ABL抑制剂的完全耐药性。在本研究中，采用等位基因特异性寡核苷酸逆转录酶聚合酶链反应分析法检测了60例伊马替尼耐药CML患者队列中的T315I突变。就疾病阶段而言，43例患者（71%）处于慢性期晚期，4例（7%）处于加速期，13例（22%）处于急变期。发现T315I突变的发生率为7%（4/60）。所有4例突变患者均处于进展期，且之前已失去所有反应。研究结果证实，该方法成本低且易于操作，可用于T315I突变筛查，阳性病例应进行直接测序以确认。
