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Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia

KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a...

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Autores principales: Jang, W, Yoon, J-H, Park, J, Lee, G D, Kim, J, Kwon, A, Choi, H, Han, K, Nahm, C H, Kim, H-J, Min, W-S, Kim, M, Kim, Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742633/
https://www.ncbi.nlm.nih.gov/pubmed/26771813
http://dx.doi.org/10.1038/bcj.2015.116
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author Jang, W
Yoon, J-H
Park, J
Lee, G D
Kim, J
Kwon, A
Choi, H
Han, K
Nahm, C H
Kim, H-J
Min, W-S
Kim, M
Kim, Y
author_facet Jang, W
Yoon, J-H
Park, J
Lee, G D
Kim, J
Kwon, A
Choi, H
Han, K
Nahm, C H
Kim, H-J
Min, W-S
Kim, M
Kim, Y
author_sort Jang, W
collection PubMed
description KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a highly sensitive allele-specific, real-time quantitative PCR (AS-qPCR) assay to analyze KIT mutations, which demonstrated excellent sensitivity and specificity. Much higher incidence of KIT mutations (62.2%, 69/111) and prevalence of multiple mutations (43.5%, 30/69) were observed using AS-qPCR, which meant the existence of multiple KIT mutant subclones. The relative KIT mutant level was variable (median, 0.3 per control allele 100 copies, 0.002–532.7) and was divided into two groups: high (⩾10, n=26) and low (<10) mutant level. Interestingly, rather than mutation positivity, mutant level was found to be associated with clinical outcome. High mutant level showed significantly inferior overall survival (P=0.005) and event-free survival (P=0.03), whereas low level did not influence the prognosis. The follow-up data showed that the mutant level were along with fusion transcripts in the majority (n=29), but moved separately in some cases, including the loss of mutations (n=5) and selective proliferation of minor clones (n=2) at relapse. This study highlighted that the KIT mutation should be analyzed using sensitive and quantitative techniques and set a cutoff level for identifying the risk group.
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spelling pubmed-47426332016-02-22 Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia Jang, W Yoon, J-H Park, J Lee, G D Kim, J Kwon, A Choi, H Han, K Nahm, C H Kim, H-J Min, W-S Kim, M Kim, Y Blood Cancer J Original Article KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a highly sensitive allele-specific, real-time quantitative PCR (AS-qPCR) assay to analyze KIT mutations, which demonstrated excellent sensitivity and specificity. Much higher incidence of KIT mutations (62.2%, 69/111) and prevalence of multiple mutations (43.5%, 30/69) were observed using AS-qPCR, which meant the existence of multiple KIT mutant subclones. The relative KIT mutant level was variable (median, 0.3 per control allele 100 copies, 0.002–532.7) and was divided into two groups: high (⩾10, n=26) and low (<10) mutant level. Interestingly, rather than mutation positivity, mutant level was found to be associated with clinical outcome. High mutant level showed significantly inferior overall survival (P=0.005) and event-free survival (P=0.03), whereas low level did not influence the prognosis. The follow-up data showed that the mutant level were along with fusion transcripts in the majority (n=29), but moved separately in some cases, including the loss of mutations (n=5) and selective proliferation of minor clones (n=2) at relapse. This study highlighted that the KIT mutation should be analyzed using sensitive and quantitative techniques and set a cutoff level for identifying the risk group. Nature Publishing Group 2016-01 2016-01-15 /pmc/articles/PMC4742633/ /pubmed/26771813 http://dx.doi.org/10.1038/bcj.2015.116 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Jang, W
Yoon, J-H
Park, J
Lee, G D
Kim, J
Kwon, A
Choi, H
Han, K
Nahm, C H
Kim, H-J
Min, W-S
Kim, M
Kim, Y
Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title_full Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title_fullStr Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title_full_unstemmed Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title_short Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
title_sort significance of kit exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742633/
https://www.ncbi.nlm.nih.gov/pubmed/26771813
http://dx.doi.org/10.1038/bcj.2015.116
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