Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia
The emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia (CML), is considered to be a feature of disease evolution. However, their frequency of incidence, impact on prognosis and treatment response effect in CML is not conclus...
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| Format: | Article |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00088/full |
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| author | Ramachandran Krishna Chandran Narayanan Geetha Kunnathur Murugesan Sakthivel Kunnathur Murugesan Sakthivel Raveendran Suresh Kumar Kumarapillai Mohanan Nair Jagathnath Krishna Hariharan Sreedharan |
| author_facet | Ramachandran Krishna Chandran Narayanan Geetha Kunnathur Murugesan Sakthivel Kunnathur Murugesan Sakthivel Raveendran Suresh Kumar Kumarapillai Mohanan Nair Jagathnath Krishna Hariharan Sreedharan |
| author_sort | Ramachandran Krishna Chandran |
| collection | DOAJ |
| description | The emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia (CML), is considered to be a feature of disease evolution. However, their frequency of incidence, impact on prognosis and treatment response effect in CML is not conclusive. In the present study, we performed a chromosome analysis of 489 patients in different clinical stages of CML, using conventional GTG-banding, Fluorescent in situ Hybridization and Spectral Karyotyping. Among the de novo CP cases, ACAs were observed in 30 patients (10.20%) with lowest incidence, followed by IM resistant CP (16.66%) whereas in AP and BC, the occurrence of ACAs were higher, and was about 40.63 and 50.98%, respectively. The frequency of occurrence of ACAs were compared between the study groups and it was found that the incidence of ACAs was higher in BC compared to de novo and IM resistant CP cases. Likewise, it was higher in AP patients when compared between de novo and IM resistant CP cases, mirroring the fact of cytogenetic evolution with disease progression in CML. In addition, we observed 10 novel and 10 rare chromosomal aberrations among the study subjects. This study pinpoints the fact that the genome of advanced phase patients was highly unstable, and this environment of genomic instability is responsible for the high occurrence of ACAs. Treatment response analysis revealed that compared to initial phases, ACAs were associated with an adverse prognostic effect during the progressive stages of CML. This study further portrayed the cytogenetic mechanism of disease evolution in CML. |
| first_indexed | 2024-12-19T23:19:17Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T23:19:17Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6d051bd32026448ca60a16ea3d4372252022-12-21T20:02:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-03-01910.3389/fonc.2019.00088435498Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous LeukemiaRamachandran Krishna Chandran0Narayanan Geetha1Kunnathur Murugesan Sakthivel2Kunnathur Murugesan Sakthivel3Raveendran Suresh Kumar4Kumarapillai Mohanan Nair Jagathnath Krishna5Hariharan Sreedharan6Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaDivision of Medical Oncology, Regional Cancer Centre, Trivandrum, IndiaLaboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaDepartment of Biochemistry, PSG College of Arts and Science, Coimbatore, IndiaLaboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaDivision of Cancer Epidemiology and Biostatistics, Regional Cancer Centre, Trivandrum, IndiaLaboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaThe emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia (CML), is considered to be a feature of disease evolution. However, their frequency of incidence, impact on prognosis and treatment response effect in CML is not conclusive. In the present study, we performed a chromosome analysis of 489 patients in different clinical stages of CML, using conventional GTG-banding, Fluorescent in situ Hybridization and Spectral Karyotyping. Among the de novo CP cases, ACAs were observed in 30 patients (10.20%) with lowest incidence, followed by IM resistant CP (16.66%) whereas in AP and BC, the occurrence of ACAs were higher, and was about 40.63 and 50.98%, respectively. The frequency of occurrence of ACAs were compared between the study groups and it was found that the incidence of ACAs was higher in BC compared to de novo and IM resistant CP cases. Likewise, it was higher in AP patients when compared between de novo and IM resistant CP cases, mirroring the fact of cytogenetic evolution with disease progression in CML. In addition, we observed 10 novel and 10 rare chromosomal aberrations among the study subjects. This study pinpoints the fact that the genome of advanced phase patients was highly unstable, and this environment of genomic instability is responsible for the high occurrence of ACAs. Treatment response analysis revealed that compared to initial phases, ACAs were associated with an adverse prognostic effect during the progressive stages of CML. This study further portrayed the cytogenetic mechanism of disease evolution in CML.https://www.frontiersin.org/article/10.3389/fonc.2019.00088/fulladditional chromosomal aberrationsvariant Ph translocationSpectral Karyotypingblast crisisfluorescent in situ hybridizationPhiladelphia Chromosome |
| spellingShingle | Ramachandran Krishna Chandran Narayanan Geetha Kunnathur Murugesan Sakthivel Kunnathur Murugesan Sakthivel Raveendran Suresh Kumar Kumarapillai Mohanan Nair Jagathnath Krishna Hariharan Sreedharan Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia Frontiers in Oncology additional chromosomal aberrations variant Ph translocation Spectral Karyotyping blast crisis fluorescent in situ hybridization Philadelphia Chromosome |
| title | Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia |
| title_full | Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia |
| title_fullStr | Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia |
| title_full_unstemmed | Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia |
| title_short | Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia |
| title_sort | impact of additional chromosomal aberrations on the disease progression of chronic myelogenous leukemia |
| topic | additional chromosomal aberrations variant Ph translocation Spectral Karyotyping blast crisis fluorescent in situ hybridization Philadelphia Chromosome |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00088/full |
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