Farhat-Maghribi Sulaf, Habbal Wafa, Monem Fawza
Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syria.
Clinical Laboratories Department, Al-Assad Hospital, Damascus University, P.O. Box 10769, Damascus, Syria.
J Oncol. 2016;2016:8420853. doi: 10.1155/2016/8420853. Epub 2016 May 30.
Background. In Syria, CML patients are started on tyrosine kinase inhibitors (TKIs) and monitored until complete molecular response is achieved. BCR-ABL mRNA transcript type is not routinely identified, contrary to the recommendations. In this study we aimed to identify the frequency of different BCR-ABL transcripts in Syrian CML patients and highlight their significance on monitoring and treatment protocols. Methods. CML patients positive for BCR-ABL transcripts by quantitative RT-PCR were enrolled. BCR-ABL transcript types were investigated using a home-made PCR method that was adapted from published protocols and optimized. The transcript types were then confirmed using a commercially available research kit. Results. Twenty-four transcripts were found in 21 patients. The most common was b2a2, followed by b3a2, b3a3, and e1a3 present solely in 12 (57.1%), 3 (14.3%), 2 (9.5%), and 1 (4.8%), respectively. Three samples (14.3%) contained dual transcripts. While b3a2 transcript was apparently associated with warning molecular response to imatinib treatment, b2a2, b3a3, and e1a3 transcripts collectively proved otherwise (P = 0.047). Conclusion. It might be advisable to identify the BCR-ABL transcript type in CML patients at diagnosis, using an empirically verified method, in order to link the detected transcript with the clinical findings, possible resistance to treatment, and appropriate monitoring methods.
背景。在叙利亚,慢性粒细胞白血病(CML)患者开始使用酪氨酸激酶抑制剂(TKIs)进行治疗,并接受监测直至达到完全分子反应。与建议相反,BCR-ABL mRNA转录本类型未常规鉴定。在本研究中,我们旨在确定叙利亚CML患者中不同BCR-ABL转录本的频率,并强调它们在监测和治疗方案中的重要性。方法。纳入通过定量逆转录聚合酶链反应(RT-PCR)检测BCR-ABL转录本呈阳性的CML患者。使用一种根据已发表方案改编并优化的自制PCR方法研究BCR-ABL转录本类型。然后使用市售研究试剂盒确认转录本类型。结果。在21例患者中发现了24种转录本。最常见的是b2a2,其次是b3a2、b3a3和e1a3,分别仅存在于12例(57.1%)、3例(14.3%)、2例(9.5%)和1例(4.8%)患者中。三个样本(14.3%)包含双重转录本。虽然b3a2转录本显然与对伊马替尼治疗的警告分子反应相关,但b2a2、b3a3和e1a3转录本总体情况并非如此(P = 0.047)。结论。在诊断时使用经验证的方法鉴定CML患者的BCR-ABL转录本类型可能是明智的,以便将检测到的转录本与临床发现、可能的治疗耐药性和适当的监测方法联系起来。