DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance
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...
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2021-09-01
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| author | Rahul Mojidra Arti Hole Keita Iwasaki Hemanth Noothalapati Tatsuyuki Yamamoto Murali Krishna C Rukmini Govekar |
| author_facet | Rahul Mojidra Arti Hole Keita Iwasaki Hemanth Noothalapati Tatsuyuki Yamamoto Murali Krishna C Rukmini Govekar |
| author_sort | Rahul Mojidra |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-b5200081c3024832a4b2d75d568019ee2023-11-22T17:44:44ZengMDPI AGCells2073-44092021-09-011010250610.3390/cells10102506DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib ResistanceRahul Mojidra0Arti Hole1Keita Iwasaki2Hemanth Noothalapati3Tatsuyuki Yamamoto4Murali Krishna C5Rukmini Govekar6Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, IndiaAdvanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, IndiaThe United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8550, JapanFaculty of Life and Environmental Sciences, Shimane University, Matsue 690-8504, JapanFaculty of Life and Environmental Sciences, Shimane University, Matsue 690-8504, JapanAdvanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, IndiaAdvanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, IndiaMonitoring 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.https://www.mdpi.com/2073-4409/10/10/2506chronic myeloid leukemiaarray comparative genomic hybridizationRaman spectroscopyresistance screeningMCR analysis |
| spellingShingle | Rahul Mojidra Arti Hole Keita Iwasaki Hemanth Noothalapati Tatsuyuki Yamamoto Murali Krishna C Rukmini Govekar DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance Cells chronic myeloid leukemia array comparative genomic hybridization Raman spectroscopy resistance screening MCR analysis |
| title | DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance |
| title_full | DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance |
| title_fullStr | DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance |
| title_full_unstemmed | DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance |
| title_short | DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance |
| title_sort | dna fingerprint analysis of raman spectra captures global genomic alterations in imatinib resistant chronic myeloid leukemia a potential single assay for screening imatinib resistance |
| topic | chronic myeloid leukemia array comparative genomic hybridization Raman spectroscopy resistance screening MCR analysis |
| url | https://www.mdpi.com/2073-4409/10/10/2506 |
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