Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation

Sigl, M; Spoerl, Silvia; Schnittger, Susanne; Meißner, Julia; Rummelt, Christoph; Peschel, Christian; Duyster, Justus; Ho, A. D.; Bubnoff, Nikolas von

doi:10.1038/bcj.2013.3

Cited by 4 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The occurrence of mutations outside the kinase domain is less frequent but could impact on TKIs resistance. Mutations on the SH domain could affect the BCR-ABL1 conformation and consequently compromise the TKI efficacy [ 42 , 43 ]. In addition to point mutations, some studies have reported resistance acquisition by abnormal splicing of BCR-ABL1 .…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia—From Molecular Mechanisms to Clinical Relevance

Alves

Gonçalves

Rutella

et al. 2021

Cancers

102

View full text Add to dashboard Cite

Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the BCR-ABL1 fusion gene, encoding the cytoplasmic chimeric BCR-ABL1 protein that displays an abnormally high tyrosine kinase activity. Although the vast majority of patients with CML respond to Imatinib, a tyrosine kinase inhibitor (TKI), resistance might occur either de novo or during treatment. In CML, the TKI resistance mechanisms are usually subdivided into BCR-ABL1-dependent and independent mechanisms. Furthermore, patients’ compliance/adherence to therapy is critical to CML management. Techniques with enhanced sensitivity like NGS and dPCR, the use of artificial intelligence (AI) techniques, and the development of mathematical modeling and computational prediction methods could reveal the underlying mechanisms of drug resistance and facilitate the design of more effective treatment strategies for improving drug efficacy in CML patients. Here we review the molecular mechanisms and other factors involved in resistance to TKIs in CML and the new methodologies to access these mechanisms, and the therapeutic approaches to circumvent TKI resistance.

show abstract

Section: Molecular Mechanismsmentioning

confidence: 99%

Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia—From Molecular Mechanisms to Clinical Relevance

Alves

Gonçalves

Rutella

et al. 2021

Cancers

102

View full text Add to dashboard Cite

show abstract

“…Nonetheless, clonal evolution may occur and erode treatment efficacy. For instance, mutations within the aberrant BCR-ABL1 fusion genes can confer resistance to imatinib mesylate and require alternative therapies (Shah et al, 2002;Sigl et al, 2013).…”

Section: Clinical Application Of Captureseqmentioning

confidence: 99%

“…However, despite a facilitated read-out and the possibility to multiplex detection of > 50 fusion variants, these assays are limited to known fusion events, and designs would require continued development to remain up-to-date (Acunzo et al, 2014;Lilljebjörn et al, 2014). In addition, PCR-based assays cannot identify small mutations within fusion products that are associated with clonal evolution and therapy unresponsiveness (O'Hare et al, 2007;Sigl et al, 2013).…”

Section: Clinical Application Of Captureseqmentioning

confidence: 99%

RNA CaptureSeq: targeted sequencing for comprehensive transcriptome studies

Brunck¹

View full text Add to dashboard Cite

rna sequencing (rnaseq) samples the majority of expressed genes infrequently, owing to the large size, complex splicing and wide dynamic range of eukaryotic transcriptomes. this results in sparse sequencing coverage that can hinder robust isoform assembly and quantification. rna capture sequencing (captureseq) addresses this challenge by using oligonucleotide probes to capture selected genes or regions of interest for targeted sequencing. targeted rnaseq provides enhanced coverage for sensitive gene discovery, robust transcript assembly and accurate gene quantification. Here we describe a detailed protocol for all stages of rna captureseq, from initial probe design considerations and capture of targeted genes to final assembly and quantification of captured transcripts. Initial probe design and final analysis can take less than 1 d, whereas the central experimental capture stage requires ~7 d.

show abstract

A thirty-five nucleotides BCR-ABL1 insertion mutation of controversial significance confers resistance to imatinib in a patient with chronic myeloid leukemia (CML)

Marcé

Cortés

Zamora

et al. 2015

Experimental and Molecular Pathology

View full text Add to dashboard Cite

Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation

Cited by 4 publications

References 8 publications

Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia—From Molecular Mechanisms to Clinical Relevance

Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia—From Molecular Mechanisms to Clinical Relevance

RNA CaptureSeq: targeted sequencing for comprehensive transcriptome studies

A thirty-five nucleotides BCR-ABL1 insertion mutation of controversial significance confers resistance to imatinib in a patient with chronic myeloid leukemia (CML)

Contact Info

Product

Resources

About