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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.241 5年影响因子: 1.349 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2018026023
pages 117-126

Prognostic Implications of Derivative Chromosome 9 Deletions in Patients with Advanced-Stage Chronic Myelogenous Leukemia

Ramachandran Krishna Chandran
Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Narayanan Geetha
Division of Medical Oncology, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Kunnathur Murugesan Sakthivel
Karunya University, Department of Biotechnology, Karunya Nagar, Coimbatore−641114, Tamil Nadu, India; Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Chandran Geetha Aswathy
Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Preethi Gopinath
Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Jagathnath Krishna Kumarapillai Mohanan Nair
Division of Cancer Epidemiology and Biostatistics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Hariharan Sreedharan
Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India

ABSTRACT

Elucidation of cryptic BCR/ABL1 gene rearrangement is exceptionally important in the clinical diagnosis and prognosis of chronic myelogenous leukemia (CML). Previous reports indicated an adverse prognostic effect of atypical BCR/ABL1 gene rearrangements with submicroscopic ABL1-BCR deletions on derivative chromosome 9 [der(9)] in CML patients. Dual color dual fusion locus-specific BCR/ABL1 fluorescent in situ hybridization (FISH) analysis together with G-banding using trypsin and Giemsa (GTG banding) was performed in 489 patients at different stages of CML to investigate the spectrum of BCR/ABL1 gene rearrangements. Among the study group analyzed, a significantly higher frequency of BCR/ABL1 gene rearrangements that is consistent with der(9) deletion were observed in the blast crisis (BC) phase at 41.67%, followed by the accelerated phase (AP) at 36.84%, the imatinib mesylate (IM)-resistant chronic phase (CP) at 23.08%, and the lowest incidence was found in de novo CP at 16.61%. 1R1G1F (1 red, 1 green, 1 fusion) with concurrent loss of ABL1-BCR fusion gene on der(9) chromosome was the major signal pattern identified in each group. The results from the current study show that this unusual BCR/ABL1 gene rearrangement is one of the steering forces toward disease progression in CML. Patients in AP/BC of CML with der(9) deletion showed poor response to IM therapy; however, patients with der(9) deletion in the early phases of CML responded well to IM treatment. Therefore, the establishment of an atypical FISH signal pattern in CML is of paramount important because it is associated with adverse clinical prognostic implications in advanced stages of the disease.


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