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慢性粒细胞白血病(CML)患者中T315I突变的定量监测。

Quantitative monitoring of the T315I mutation in patients with chronic myeloid leukemia (CML).

作者信息

Chomel Jean-Claude, Sorel Nathalie, Bonnet Marie-Laure, Bertrand Angelina, Brizard Françoise, Saulnier Pierre-Jean, Roy Lydia, Guilhot François, Turhan Ali G

机构信息

Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, France.

出版信息

Leuk Res. 2009 Apr;33(4):551-5. doi: 10.1016/j.leukres.2008.08.018. Epub 2008 Sep 30.

Abstract

Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). However, resistances are occasionally observed, mainly due to mutations within the BCR-ABL kinase domain. The T315I substitution confers complete resistance to TKIs commonly used in clinical practice. In the present study, we used an allele-specific quantitative-RT-PCR to perform a molecular follow-up of BCR-ABL transcripts harboring the T315I mutation. We retrospectively quantified BCR-ABL315I mRNA in five patients who acquired the T315I mutation. Our results highlight the relevance of allele-specific Q-RT-PCR experiments for the monitoring of mutated BCR-ABL transcripts and suggest that the kinetics of emergence of T315I mutant mRNA is influenced by the stage of the disease and the presence of previous BCR-ABL kinase domain mutations.

摘要

酪氨酸激酶抑制剂(TKIs)显著改善了慢性髓性白血病(CML)的治疗。然而,偶尔会观察到耐药性,主要是由于BCR-ABL激酶结构域内的突变。T315I替代赋予对临床实践中常用TKIs的完全耐药性。在本研究中,我们使用等位基因特异性定量逆转录PCR对携带T315I突变的BCR-ABL转录本进行分子随访。我们回顾性地定量了五名发生T315I突变患者的BCR-ABL315I mRNA。我们的结果突出了等位基因特异性定量逆转录PCR实验对监测突变BCR-ABL转录本的相关性,并表明T315I突变体mRNA出现的动力学受疾病阶段和先前BCR-ABL激酶结构域突变的影响。

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