Abstract:
INTRODUCTION:Multiple types of mutations in the BCR-ABL1 kinase domain have been reported. We previously reported a common alternatively spliced BCR-ABL mRNA with a 35-nucleotide insertion (35INS). We report three novel alternative splicing mutants expressed as the dominant transcripts in patient with chronic myelogenous leukemia and resistance to kinase inhibitors. METHODS:We screened RNA from more than 200 patients with resistance to more than one of the three kinase inhibitors for ABL1 kinase domain mutations by direct sequencing. RESULTS:We found three not previously described splice mutants. All three showed >90% mutant transcript. The first resulted from the insertion of 79 nucleotides into the ABL1 exon 8-9 junction. The inserted sequence contained a sequence from regions of intron 8, located 120 bp apart: the 35-nucleotide sequence previously described, and an additional 44-nucleotide segment downstream from 35INS. The combined 79-nucleotide insertion splice mutant showed the same protein change as 35INS (p C475YfsX11). The second splice mutation comprised an 84-nucleotide sequence from intron 7 inserted into the ABL1 exon7-8 junction, also causing a frameshift and protein truncation (p A424EfsX18). The third splice derived from a 231-nucleotide sequence from intron 4 retained in the ABL1 exon 4-5 junction adding 40 intron-encoded amino acids and leading to a frameshift and early termination (p E275LfsX41). CONCLUSION:These findings, when combined with the data on 35INS, support the concept that loss of the C-terminus of BCR-ABL1 is associated with significant resistance to kinase inhibitors; this mechanism appears to be a major source of resistance to kinase inhibitors.
journal_name
Int J Lab Hematoljournal_title
International journal of laboratory hematologyauthors
Ma W,Giles F,Zhang X,Wang X,Zhang Z,Lee TS,Yeh CH,Albitar Mdoi
10.1111/j.1751-553X.2010.01291.xsubject
Has Abstractpub_date
2011-06-01 00:00:00pages
326-31issue
3eissn
1751-5521issn
1751-553Xjournal_volume
33pub_type
杂志文章abstract::Congenital protein C deficiency significantly increases the risk of venous thromboembolism, a serious and potentially lethal condition. Protein C levels can be determined by chromogenic, clotting and antigenic assays, each type of assay has differences in specificity and sensitivity to protein C deficiency. In princip...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
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journal_title:International journal of laboratory hematology
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2009.01178.x
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abstract::Multiple myeloma (MM) is a malignant plasma cell disorder that involves multiple genetic abnormalities. Chimeric transcription factors, created by gene fusion as a result of chromosomal translocations, have been implicated in the pathogenesis of the disease. Here, we report the conventional cytogenetic analysis of a M...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2006.00837.x
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2012.01450.x
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abstract::Bone marrow aspiration and biopsy can be a painful procedure. Sedation techniques may make this investigation more acceptable to patients, but have the potential to cause life-threatening complications, as well as requiring additional staff and equipment for safe administration. We assessed the use of Entonox, a 50 : ...
journal_title:International journal of laboratory hematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1751-553X.2007.00905.x
更新日期:2008-02-01 00:00:00
abstract:INTRODUCTION:In order to correctly manage the paediatric patients affected with haemostatic disorders, age-appropriate reference intervals should be used. The purpose of this study was to establish age-specific reference intervals for prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (aPT...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2011.01384.x
更新日期:2012-06-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
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abstract::Treatment of malignant blood disorders, such as leukemia, that can provide a better chance of long-term remission involves myeloablation followed by transplantation of matched donor hematopoietic stem cells (HSCs). For successful engraftment and re-establishment of hematopoiesis to occur in the recipient, the transpla...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/j.1751-553X.2010.01250.x
更新日期:2010-12-01 00:00:00
abstract::The ongoing COVID-19 pandemic has had a profound worldwide impact on the laboratory hematology community. Nevertheless, the pace of COVID-19 hematology-related research has continued to accelerate and has established the role of laboratory hematology data for many purposes including disease prognosis and outcome. The ...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/ijlh.13381
更新日期:2020-11-12 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2012.01400.x
更新日期:2012-08-01 00:00:00
abstract:INTRODUCTION:Participation in external quality assessment (EQA) is central to the maintenance of high-quality laboratory results in patient diagnosis and clinical trials. Laboratories in the TAF112582 DETECTIVE study (ClinicalTrials.gov identifier: NCT01376167) are enrolled in the United Kingdom National Quality Assess...
journal_title:International journal of laboratory hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/ijlh.12627
更新日期:2017-06-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
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更新日期:2020-06-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/ijlh.12516
更新日期:2016-08-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/ijlh.13095
更新日期:2019-10-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2012.01406.x
更新日期:2012-08-01 00:00:00
abstract::In the 8 years since the publication of the 4th edition of the WHO Classification of Hematopoietic and Lymphoid Tumours in 2008, there has been rapid accumulation of knowledge in the molecular genetics, biology, clinical behavior of many hematologic malignancies. Concepts and models have advanced to the point at which...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
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更新日期:2017-05-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章,多中心研究
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章,实务指引
doi:10.1111/j.1751-553X.2011.01367.x
更新日期:2012-02-01 00:00:00
abstract::Platelets play a central role in physiological hemostasis and also in pathological thrombosis. It is well established that congenital or acquired abnormalities of platelet function are associated with a heightened risk of bleeding of variable severity and excessive hemorrhage after surgery or trauma. Several kinds of ...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
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更新日期:2016-05-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/ijlh.12083
更新日期:2013-06-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/j.1751-553X.2010.01275.x
更新日期:2011-04-01 00:00:00
abstract::Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor ...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/ijlh.12220
更新日期:2014-06-01 00:00:00
abstract:INTRODUCTION:Cellular analysis in body fluids (BFs) provides important diagnostic information in various pathological settings. This study was hence aimed at comparing automated cell count obtained with Mindray BC-6800 (BC-BF) vs Sysmex XN-series (XN-BF) and evaluating other quantitative and qualitative information pro...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/ijlh.12968
更新日期:2019-04-01 00:00:00
abstract::The majority, if not all, of human cell types secrete extracellular vesicles (EVs) into their environment, at least partly as a means of intercellular communication. These secreted vesicles can be detected in most bodily fluids including blood, urine, and saliva. The number of secreted vesicles and their composition i...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/ijlh.12247
更新日期:2014-06-01 00:00:00
abstract:INTRODUCTION:The Hematoflow (Beckman Coulter, USA) is a new automated hematology analyzer, which provides a 16-part white blood cell count (WBC) differential. METHODS:We evaluated the differential WBC count performance of the Hematoflow. 101 blood samples from patients were selected for comparison analysis. RESULTS:T...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/j.1751-553X.2012.01432.x
更新日期:2012-10-01 00:00:00
abstract:INTRODUCTION:It is widely recognized that plasma cells (PCs) are under-represented in flow cytometry (FC) studies, but the causes of this phenomenon are poorly understood. We sought to study potential variables that affect PC recovery by flow cytometry (FC) in the analysis of plasma cell myeloma (PCM). METHODS:We retr...
journal_title:International journal of laboratory hematology
pub_type: 杂志文章
doi:10.1111/ijlh.12411
更新日期:2015-12-01 00:00:00
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journal_title:International journal of laboratory hematology
pub_type: 杂志文章,评审
doi:10.1111/ijlh.12822
更新日期:2018-05-01 00:00:00