Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, India.
Homi Bhabha National Institute, BARC Training School Complex, Mumbai 400094, India.
Cells. 2021 Sep 22;10(10):2506. doi: 10.3390/cells10102506.
Monitoring the development of resistance to the tyrosine kinase inhibitor (TKI) imatinib in chronic myeloid leukemia (CML) patients in the initial chronic phase (CP) is crucial for limiting the progression of unresponsive patients to terminal phase of blast crisis (BC). This study for the first time demonstrates the potential of Raman spectroscopy to sense the resistant phenotype. Currently recommended resistance screening strategy include detection of BCR-ABL1 transcripts, kinase domain mutations, complex chromosomal abnormalities and BCR-ABL1 gene amplification. The techniques used for these tests are expensive, technologically demanding and have limited availability in resource-poor countries. In India, this could be a reason for more patients reporting to clinics with advanced disease. A single method which can identify resistant cells irrespective of the underlying mechanism would be a practical screening strategy. During our analysis of imatinib-sensitive and -resistant K562 cells, by array comparative genomic hybridization (aCGH), copy number variations specific to resistant cells were detected. aCGH is technologically demanding, expensive and therefore not suitable to serve as a single economic test. We therefore explored whether DNA finger-print analysis of Raman hyperspectral data could capture these alterations in the genome, and demonstrated that it could indeed segregate imatinib-sensitive and -resistant cells. Raman spectroscopy, due to availability of portable instruments, ease of spectrum acquisition and possibility of centralized analysis of transmitted data, qualifies as a preliminary screening tool in resource-poor countries for imatinib resistance in CML. This study provides a proof of principle for a single assay for monitoring resistance to imatinib, available for scrutiny in clinics.
监测慢性髓性白血病（CML）初诊慢性期（CP）患者对酪氨酸激酶抑制剂（TKI）伊马替尼的耐药发展对于限制无应答患者向急变期进展至关重要。本研究首次证明了拉曼光谱在检测耐药表型方面的潜力。目前推荐的耐药筛选策略包括检测 BCR-ABL1 转录本、激酶结构域突变、复杂染色体异常和 BCR-ABL1 基因扩增。这些检测方法的技术昂贵，技术要求高，在资源匮乏的国家可用性有限。在印度，这可能是更多患者报告患有晚期疾病的原因。无论潜在机制如何，能够识别耐药细胞的单一方法将是一种实用的筛选策略。在对伊马替尼敏感和耐药的 K562 细胞进行分析时，我们通过 array 比较基因组杂交（aCGH）检测到了耐药细胞特有的拷贝数变异。aCGH 技术要求高，成本昂贵，因此不适合作为单一的经济检测方法。因此，我们探讨了拉曼高光谱数据的 DNA 指纹分析是否可以捕获这些基因组中的改变，并证明它确实可以分离伊马替尼敏感和耐药的细胞。拉曼光谱由于便携式仪器的可用性、光谱采集的简便性以及传输数据的集中分析的可能性，因此有资格成为资源匮乏国家 CML 中伊马替尼耐药的初步筛选工具。本研究为监测伊马替尼耐药的单一检测提供了原理证明，可在临床中进行审查。
