{"title":"KIT 突变转录本水平对监测 t(8;21)型急性髓性白血病可测量残留疾病的有用性。","authors":"Yuan Sun, Xu Wang, Wen-Min Chen, Yue Hao, Ling-Di Li, Jin-Ying Li, Kai Sun, Zong-Yan Shi, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin","doi":"10.1002/hon.3264","DOIUrl":null,"url":null,"abstract":"<p>In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT<sup>mut</sup>) DNA level is reportedly predictive of relapse in <i>t</i> (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT<sup>mut</sup> transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 <i>t</i> (8; 21) AML patients with KIT<sup>mut</sup> (D816V/H/Y or N822K) were tested for KIT<sup>mut</sup> transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT<sup>mut</sup> were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT<sup>mut</sup>-high (KIT_H) group and the KIT<sup>mut</sup>-low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (<i>p</i> = 0.0040 and 0.021, respectively) and Course 2 consolidation (<i>p</i> = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT<sup>mut</sup> and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in <i>t</i> (8; 21) AML patient with KIT mutation.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia\",\"authors\":\"Yuan Sun, Xu Wang, Wen-Min Chen, Yue Hao, Ling-Di Li, Jin-Ying Li, Kai Sun, Zong-Yan Shi, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin\",\"doi\":\"10.1002/hon.3264\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT<sup>mut</sup>) DNA level is reportedly predictive of relapse in <i>t</i> (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT<sup>mut</sup> transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 <i>t</i> (8; 21) AML patients with KIT<sup>mut</sup> (D816V/H/Y or N822K) were tested for KIT<sup>mut</sup> transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT<sup>mut</sup> were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT<sup>mut</sup>-high (KIT_H) group and the KIT<sup>mut</sup>-low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (<i>p</i> = 0.0040 and 0.021, respectively) and Course 2 consolidation (<i>p</i> = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT<sup>mut</sup> and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in <i>t</i> (8; 21) AML patient with KIT mutation.</p>\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"42 2\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-03-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.3264\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.3264","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia
In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut-high (KIT_H) group and the KITmut-low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.
期刊介绍:
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.