Chomel Jean-Claude, Sorel Nathalie, Bonnet Marie-Laure, Bertrand Angelina, Brizard Françoise, Saulnier Pierre-Jean, Roy Lydia, Guilhot François, Turhan Ali G
Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, France.
Leuk Res. 2009 Apr;33(4):551-5. doi: 10.1016/j.leukres.2008.08.018. Epub 2008 Sep 30.
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.
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。