Department of Molecular Biology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan.
Department of Transplant Immunology and Applied Microbiology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan.
BMC Cancer. 2022 May 8;22(1):519. doi: 10.1186/s12885-022-09605-1.
Cytochrome P450 (CYP) and glutathione S transferases (GSTs) are important biotransforming enzymes responsible for detoxification of anticancer drugs and carcinogens. Polymorphisms in these enzymes may greatly influence the susceptibility to CML and overall efficacy of tyrosine kinase inhibitors. This study was aimed to estimate the possible influence of the polymorphisms of GSTs and CYP in the occurrence of CML as well as in predicting therapeutic outcome of nilotinib therapy in Pakistani CML patients.
The polymorphic variability in CYP 1A1*2C, GSTP1 (A3131G), GSTT1 and GSTM1 was assessed either by RFLP or multiplex PCR. The BCR ABL1 transcripts were quantified by qPCR to monitor response to nilotinib.
The CYP1A1*2C heterozygous and GSTP1 homozygous polymorphisms seemed to be a contributing factor in developing CML. Altogether, there were 12 non-responders, 66 responders and 21 partial responders. The most frequent genotype was null GSTM1 in responders followed by CYP 1A1 and GSTP1 -wild type (p = < 0.05). Whereas, homozygous GSTP1 and GSTT1 null genotype is significantly higher only among nilotinib non-responders.
Hence, it can be concluded that wild type CYP1A1, GSTP1 and null GSTM1 may be frequently linked to favorable outcome in patients treated with nilotinib as depicted by sustained deep molecular response in most CML patients.
细胞色素 P450（CYP）和谷胱甘肽 S 转移酶（GSTs）是重要的生物转化酶，负责解毒抗癌药物和致癌物。这些酶的多态性可能极大地影响 CML 的易感性和酪氨酸激酶抑制剂的总体疗效。本研究旨在评估 GSTs 和 CYP 的多态性对 CML 发生的可能影响，以及对巴基斯坦 CML 患者尼洛替尼治疗疗效的预测。
通过 RFLP 或多重 PCR 评估 CYP1A1*2C、GSTP1（A3131G）、GSTT1 和 GSTM1 的多态性变异性。通过 qPCR 定量 BCR ABL1 转录本，以监测对尼洛替尼的反应。
CYP1A1*2C 杂合和 GSTP1 纯合多态性似乎是导致 CML 发生的因素之一。共有 12 名无应答者、66 名应答者和 21 名部分应答者。最常见的基因型是应答者中的空 GSTM1，其次是 CYP 1A1 和 GSTP1-野生型（p<0.05）。然而，仅在尼洛替尼无应答者中，GSTP1 和 GSTT1 纯合空基因型显著更高。
因此，可以得出结论，野生型 CYP1A1、GSTP1 和空 GSTM1 可能与尼洛替尼治疗患者的良好结局相关，因为大多数 CML 患者的持续深度分子反应表明了这一点。
