Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identification of BCR-ABL1 fusion gene amplification status is critically important in the effective management of chronic myelogenous leukemia (CML) patients. Earlier reports suggested that overexpression of BCR-ABL1 either through amplification of BCR-ABL1 fusion gene or by the up regulation of BCR-ABL1 transcript level might be an early phenomenon in the establishment of IM resistance and disease evolution in CML. In the current study, we performed dual color dual fusion locus specific BCR/ABL1 FISH analysis along with karyotype analysis using GTG banding (G-banding using trypsin and Giemsa) technique in 489 patients with different clinical stages of CML at diagnosis or during the course of the disease to unravel the spectrum of BCR-ABL1 fusion gene amplification status. Among the study group analyzed, it was found that prevalence of occurrence of BCR-ABL1 fusion gene amplification was significantly higher in advanced stages of disease and in IM resistant CML-CP patients when compared to initial stage of disease, de novo CML-CP. Cytogenetic and metaphase FISH characterization on our study samples revealed that BCR-ABL1 fusion gene amplification was occurred through the formation of extra copies Ph chromosomes and isoderived Ph chromosomes. Current study suggests that unrestrained activity of BCR-ABL1 played a vital role in resistance to targeted therapy and disease evolution in CML. In our study population, patients in progressive stage CML and in IM resistant CP with multiple copies of BCR-ABL1 fusion gene displayed a poor response to targeted treatment with IM. Hence, the early identification of BCR-ABL1 fusion gene amplification using FISH technique will lead to improved interventions and outcome in future CML patients.
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PMID:Genomic amplification of BCR-ABL1 fusion gene and its impact on the disease progression mechanism in patients with chronic myelogenous leukemia. 3039 26

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.
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PMID:Impact of Additional Chromosomal Aberrations on the Disease Progression of Chronic Myelogenous Leukemia. 3089 24


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