Breakpoint mapping of a t(9;22;12) chronic myeloid leukaemia patient with e14a3 BCR‐ABL1 transcript using Nanopore sequencing

Zhao, H.; Chen, Yuan; Shen, Cong; Li, Lingshu; Li, Qingzhao; Tan, Kui; Huang, Huang; Hu, Guoyu

doi:10.1002/jgm.3276

Cited by 8 publications

(4 citation statements)

References 62 publications

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“…In addition, we also reviewed the references of the retrieved literature. Currently, 62 cases with e14a3 (b3a3) transcripts were reported, including our present patient, of which 25 cases had relatively detailed information of the clinical characteristics and treatments ( Table 2 ) [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Notably, male patients accounted for 84% (21/25) of the CML cases with the e14a3 (b3a3) transcript, which was consistent with previous studies [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report

Zhang¹,

Sun²,

Su³

et al. 2022

Current Oncology

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An atypical BCR::ABL1 fusion gene transcript in chronic myeloid leukemia (CML) patients, even those with variant Philadelphia (Ph) chromosome translocation, is very rare. In the present study, we report a case of CML (41 years, female) with extreme thrombocytosis at onset, with the variant Ph chromosome and rare e14a3 (b3a3) BCR::ABL1 transcript. The patient was prescribed imatinib as a first-line therapy and subsequently achieved complete hematologic remission within 2 months and major molecular response (MMR) within 3 months, and the transcript was undetectable within half a year. During up to nine years of follow-up, the quantification of this rare fusion gene was consistently negative with no BCR::ABL1 kinase domain mutations. Furthermore, we collected previously reported CML cases with the e14a3 (b3a3) transcript that indicated that the e14a3 (b3a3) transcripts appeared to have a larger number of thrombocytosis and variant Ph translocations than CML in general. This subgroup of CML might have better responses and outcomes to imatinib than patients with common transcripts.

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Section: Discussionmentioning

confidence: 99%

Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report

Zhang¹,

Sun²,

Su³

et al. 2022

Current Oncology

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“…Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL, has shown remarkable clinical activity in patients with CML [ 155 ]. Several studies have reported that PacBio sequencing and ONT sequencing can be applied to detect BCR-ABL1 fusion events and related tyrosine kinase inhibitor (TKI) resistance mutations in samples from CML patients both at diagnosis and during follow-up [ 156 ], [ 157 ], [ 158 ]. These technologies are also important for identifying other components involved in CML pathogenesis to can be exploited to overcome tyrosine kinase inhibitors (TKI) resistance.…”

Section: Applications Of Tgs Technologies In Cancermentioning

confidence: 99%

Application of third-generation sequencing in cancer research

Chen

2021

Medical Review

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In the past several years, nanopore sequencing technology from Oxford Nanopore Technologies (ONT) and single-molecule real-time (SMRT) sequencing technology from Pacific BioSciences (PacBio) have become available to researchers and are currently being tested for cancer research. These methods offer many advantages over most widely used high-throughput short-read sequencing approaches and allow the comprehensive analysis of transcriptomes by identifying full-length splice isoforms and several other posttranscriptional events. In addition, these platforms enable structural variation characterization at a previously unparalleled resolution and direct detection of epigenetic marks in native DNA and RNA. Here, we present a comprehensive summary of important applications of these technologies in cancer research, including the identification of complex structure variants, alternatively spliced isoforms, fusion transcript events, and exogenous RNA. Furthermore, we discuss the impact of the newly developed nanopore direct RNA sequencing (RNA-Seq) approach in advancing epitranscriptome research in cancer. Although the unique challenges still present for these new single-molecule long-read methods, they will unravel many aspects of cancer genome complexity in unprecedented ways and present an encouraging outlook for continued application in an increasing number of different cancer research settings.

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“…Chronic myeloid leukaemia (CML), a subtype of myeloproliferative neoplasm (MPN), is characterized by the translocation t(9;22)(q34;q11), the Philadelphia (Ph) chromosome [1]. The resulting breakpoint cluster region (BCR)::Abelson (ABL) chimeric protein which stimulates high levels of protein kinase activity is a hallmark of the leukemogenesis in CML patients [2,3].…”

Section: Introductionmentioning

confidence: 99%

The study of the impact of additional chromosomal aberrations and c-MYC and BCR::ABL1 genes amplification on CML patient’s characteristics: relation to haematological parameters and patient outcome

Attia,

Fouad,

Samy

2023

Egypt J Med Hum Genet

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Background Chronic myeloid leukaemia is characterised by genetic instability which results in additional cytogenetic aberrations that have been linked to progression to advanced phase. Genomic study linked amplified genes in the form of c-MYC and/or the rare BCR::ABL1 genes amplification to chronic myeloid leukaemia. The effect of these genes’ amplification on patients’ characteristics and disease progression still needs further study. This cross-sectional study aimed to investigate the frequency of additional chromosomal aberrations in addition to c-MYC and BCR::ABL1 genes amplification in chronic myeloid leukaemia patients and their impact on patient’s characteristics, disease progression, and level of remission. The study included cytogenetic analysis of 49 Philadelphia positive chronic myeloid leukaemia patients and investigation of c-MYC and BCR::ABL1 genes amplification by fluorescence in situ hybridization. Results Patients with additional chromosomal aberrations represented 36.7% and had significantly lower platelet count (P = 0.003) and higher blast count (P = 0.008). The acquisition of additional chromosomal aberrations was significantly higher in chronic myeloid leukaemia patients with advanced stages (P = 0.014). Follow-up of the patients for 6 months revealed significant higher frequency of additional chromosomal aberrations in patients with failure of remission (P < 0.0001). A highly significant association between cases with failure of molecular remission (P = 0.001) and co-existing additional chromosomal aberrations. Amplification of the c-MYC gene was detected in 6 cases. The cases with c-MYC amplification showed significantly higher peripheral blood and bone marrow blasts (P = 0.029 and P = 0.008, respectively) and significantly lower platelet count (P = 0.044). Amplification of c-MYC was significantly associated with additional chromosomal aberrations (P = 0.011). Molecular remission was not achieved in any of the instances with c-MYC amplification. A highly significant association between c-MYC amplification and poor patient outcome was detected (P = 0.002). BCR::ABL1 amplification was detected in three cases, and ABL amplification was detected in four cases. Patients with BCR::ABL1 amplification showed significantly higher blast count. BCR::ABL1 amplification was significantly associated with disease progression and failure of molecular remission (P = 0.002). Conclusion Additional chromosomal aberrations, c-MYC amplification, and BCR:ABL1 amplification in chronic myeloid leukaemia stratify patients with disease progression, which may lead to better interventions and improved outcome in the future chronic myeloid leukaemia patients.

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Breakpoint mapping of a t(9;22;12) chronic myeloid leukaemia patient with e14a3 BCR‐ABL1 transcript using Nanopore sequencing

Cited by 8 publications

References 62 publications

Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report

Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report

Application of third-generation sequencing in cancer research

The study of the impact of additional chromosomal aberrations and c-MYC and BCR::ABL1 genes amplification on CML patient’s characteristics: relation to haematological parameters and patient outcome

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