Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia

• Published in: Frontiers in oncology Vol. 9; p. 88
• Main Authors: Krishna Chandran, Ramachandran, Geetha, Narayanan, Sakthivel, Kunnathur Murugesan, Suresh Kumar, Raveendran, Jagathnath Krishna, Kumarapillai Mohanan Nair, Sreedharan, Hariharan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 05.03.2019
• Subjects: additional chromosomal aberrations; blast crisis; fluorescent in situ hybridization; Oncology; Philadelphia Chromosome; Spectral Karyotyping; variant Ph translocation; fluorescent in situ hybridization; GTG-banding; Spectral Karyotyping; additional chromosomal aberrations; chronic myeloid leukemia; variant Ph translocation; Philadelphia Chromosome; blast crisis
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.00088

The emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/ 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 Hybridization and Spectral Karyotyping. Among the 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 and IM resistant CP cases. Likewise, it was higher in AP patients when compared between 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.