Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India.
Division of Medical Oncology, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India.
Blood Cells Mol Dis. 2019 Jul;77:51-60. doi: 10.1016/j.bcmd.2019.03.004. Epub 2019 Mar 24.
The molecular mechanisms responsible for disease progression of CML are not conclusive. The main functional changes associated with disease evolution in CML was high proliferation rate, decreased apoptosis, blockade of differentiation, and strong resistance to chemotherapeutic agents. The current study analyzed the relative expressional profiles of genes related with proliferation, apoptosis, differentiation, and resistance to chemotherapeutic agents such as c-MYC, BAD, BCL-2, C/EBPα/-β and ABCB1 respectively in different clinical stages of CML by SYBR Green I quantitative real-time (qRT) PCR. We selected a total of 183 CML patients and 30 healthy control samples. The study populations were classified into four groups, including de novo CML-CP (50/183), CML-AP (32/183), CML-BC (51/183) and Imatinib Mesylate or IM resistant CML-CP (50/183) groups. qRT PCR analysis revealed that significant overexpression of c-MYC, ABCB1 and BCL-2 was observed in advanced phases and IM resistant CP of CML compared to healthy controls. Likewise, the mean expression level of BAD, C/EBPα/-β genes were found to be significantly down regulated. Present study concluded that the complex interplay of several candidate genes like overexpression of c-MYC, ABCB1, BCL-2 and down regulation of BAD, C/EBPα/-β played a significant role in the disease evolution and development of drug resistant in CML.
导致 CML 疾病进展的分子机制尚不完全清楚。与 CML 疾病演变相关的主要功能变化是高增殖率、凋亡减少、分化阻滞和对化疗药物的强耐药性。本研究通过 SYBR Green I 定量实时(qRT)PCR 分析了不同临床阶段 CML 中与增殖、凋亡、分化和耐药相关的基因(如 c-MYC、BAD、BCL-2、C/EBPα/-β 和 ABCB1)的相对表达谱。我们选择了总共 183 名 CML 患者和 30 名健康对照样本。研究人群分为四组,包括初诊 CML-CP(50/183)、CML-AP(32/183)、CML-BC(51/183)和伊马替尼耐药 CML-CP(50/183)组。qRT-PCR 分析显示,与健康对照组相比,晚期 CML 和伊马替尼耐药 CP 中 c-MYC、ABCB1 和 BCL-2 的表达明显上调。同样,BAD、C/EBPα/-β 基因的平均表达水平也明显下调。本研究得出结论,c-MYC、ABCB1、BCL-2 的过表达和 BAD、C/EBPα/-β 的下调等几个候选基因的复杂相互作用在 CML 的疾病演变和耐药发展中起重要作用。