Prognostic Implications of Derivative Chromosome 9 Deletions in Patients with Advanced-Stage Chronic Myelogenous Leukemia
| Autor: | Kunnathur Murugesan Sakthivel, Preethi Gopinath, Narayanan Geetha, Ramachandran Krishna Chandran, Chandran Geetha Aswathy, Hariharan Sreedharan, Jagathnath Krishna Kumarapillai Mohanan Nair |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Derivative chromosome Adolescent Health Toxicology and Mutagenesis Toxicology Pathology and Forensic Medicine Fusion gene Young Adult hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive Medicine Humans In Situ Hybridization Fluorescence Aged Aged 80 and over Gene Rearrangement ABL medicine.diagnostic_test business.industry breakpoint cluster region General Medicine Gene rearrangement Middle Aged medicine.disease Prognosis Imatinib mesylate Cancer research Female Chromosome Deletion business Chromosomes Human Pair 9 Chronic myelogenous leukemia Fluorescence in situ hybridization |
| Zdroj: | Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer. 37(2) |
| ISSN: | 2162-6537 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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