{"title":"慢性髓性白血病BCR::ABL1酪氨酸激酶结构域突变筛查的定制质谱阵列面板","authors":"Nittaya Limsuwanachot , Budsaba Rerkamnuaychoke , Pimjai Niparuck , Roongrudee Singdong , Adcharee Kongruang , Piyapha Hirunpatrawong , Thanaporn Siriyakorn , Pa-thai Yenchitsomanus , Teerapong Siriboonpiputtana","doi":"10.1016/j.jmsacl.2023.04.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>The therapeutic strategy and management of chronic myeloid leukemia (CML) have rapidly improved with the discovery of effective tyrosine kinase inhibitors (TKIs) to target BCR::ABL1 oncoprotein. However, nearly 30% of patients develop TKI resistance due to acquired mutations on the tyrosine kinase domain (TKD) of <em>BCR</em>::<em>ABL1</em>.</p></div><div><h3>Methods</h3><p>We customized a mass array panel initially intended to detect and monitor the mutational burden of hotspot <em>BCR</em>::<em>ABL1</em> TKD mutations accumulated in our database, including key mutations recently recommended by European LeukemiaNet. Additionally, we extended the feasibility of using the assay panel for the molecular classification of myeloproliferative neoplasms (MPNs) by incorporating primer sets specific for analyzing <em>JAK2</em> V617F, <em>MPL</em> 515 K/L, and <em>CALR</em> types 1 and 2.</p></div><div><h3>Results</h3><p>We found that the developed mass array panel was superior for detecting and monitoring clinically significant <em>BCR</em>::<em>ABL1</em> TKD mutations, especially in cases with low mutational burden and harboring compound/polyclonal mutations, compared with direct sequencing. Moreover, our customized mass array panel detected common genetic alterations in MPNs, and the findings were consistent with those of other comparable assays available in our laboratory.</p></div><div><h3>Conclusions</h3><p>Our customized mass array panel was practicably used as a routine robust assay for screening and monitoring <em>BCR</em>::<em>ABL1</em> TKD mutations in patients with CML undergoing TKI treatment and feasible for analyzing common genetic mutations in MPNs.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 122-132"},"PeriodicalIF":3.1000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A customized mass array panel for BCR::ABL1 tyrosine kinase domain mutation screening in chronic myeloid leukemia\",\"authors\":\"Nittaya Limsuwanachot , Budsaba Rerkamnuaychoke , Pimjai Niparuck , Roongrudee Singdong , Adcharee Kongruang , Piyapha Hirunpatrawong , Thanaporn Siriyakorn , Pa-thai Yenchitsomanus , Teerapong Siriboonpiputtana\",\"doi\":\"10.1016/j.jmsacl.2023.04.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>The therapeutic strategy and management of chronic myeloid leukemia (CML) have rapidly improved with the discovery of effective tyrosine kinase inhibitors (TKIs) to target BCR::ABL1 oncoprotein. However, nearly 30% of patients develop TKI resistance due to acquired mutations on the tyrosine kinase domain (TKD) of <em>BCR</em>::<em>ABL1</em>.</p></div><div><h3>Methods</h3><p>We customized a mass array panel initially intended to detect and monitor the mutational burden of hotspot <em>BCR</em>::<em>ABL1</em> TKD mutations accumulated in our database, including key mutations recently recommended by European LeukemiaNet. Additionally, we extended the feasibility of using the assay panel for the molecular classification of myeloproliferative neoplasms (MPNs) by incorporating primer sets specific for analyzing <em>JAK2</em> V617F, <em>MPL</em> 515 K/L, and <em>CALR</em> types 1 and 2.</p></div><div><h3>Results</h3><p>We found that the developed mass array panel was superior for detecting and monitoring clinically significant <em>BCR</em>::<em>ABL1</em> TKD mutations, especially in cases with low mutational burden and harboring compound/polyclonal mutations, compared with direct sequencing. Moreover, our customized mass array panel detected common genetic alterations in MPNs, and the findings were consistent with those of other comparable assays available in our laboratory.</p></div><div><h3>Conclusions</h3><p>Our customized mass array panel was practicably used as a routine robust assay for screening and monitoring <em>BCR</em>::<em>ABL1</em> TKD mutations in patients with CML undergoing TKI treatment and feasible for analyzing common genetic mutations in MPNs.</p></div>\",\"PeriodicalId\":52406,\"journal\":{\"name\":\"Journal of Mass Spectrometry and Advances in the Clinical Lab\",\"volume\":\"28 \",\"pages\":\"Pages 122-132\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Mass Spectrometry and Advances in the Clinical Lab\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667145X23000238\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Mass Spectrometry and Advances in the Clinical Lab","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667145X23000238","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
A customized mass array panel for BCR::ABL1 tyrosine kinase domain mutation screening in chronic myeloid leukemia
Introduction
The therapeutic strategy and management of chronic myeloid leukemia (CML) have rapidly improved with the discovery of effective tyrosine kinase inhibitors (TKIs) to target BCR::ABL1 oncoprotein. However, nearly 30% of patients develop TKI resistance due to acquired mutations on the tyrosine kinase domain (TKD) of BCR::ABL1.
Methods
We customized a mass array panel initially intended to detect and monitor the mutational burden of hotspot BCR::ABL1 TKD mutations accumulated in our database, including key mutations recently recommended by European LeukemiaNet. Additionally, we extended the feasibility of using the assay panel for the molecular classification of myeloproliferative neoplasms (MPNs) by incorporating primer sets specific for analyzing JAK2 V617F, MPL 515 K/L, and CALR types 1 and 2.
Results
We found that the developed mass array panel was superior for detecting and monitoring clinically significant BCR::ABL1 TKD mutations, especially in cases with low mutational burden and harboring compound/polyclonal mutations, compared with direct sequencing. Moreover, our customized mass array panel detected common genetic alterations in MPNs, and the findings were consistent with those of other comparable assays available in our laboratory.
Conclusions
Our customized mass array panel was practicably used as a routine robust assay for screening and monitoring BCR::ABL1 TKD mutations in patients with CML undergoing TKI treatment and feasible for analyzing common genetic mutations in MPNs.