Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A
Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. Twenty-seven AML patients with normal karyotype but beari...
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Published in | Annals of laboratory medicine Vol. 36; no. 5; pp. 399 - 404 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Korea (South)
The Korean Society for Laboratory Medicine
01.09.2016
대한진단검사의학회 |
Subjects | |
Online Access | Get full text |
ISSN | 2234-3806 2234-3814 2234-3814 |
DOI | 10.3343/alm.2016.36.5.399 |
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Abstract | Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose.
Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared.
The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis.
The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation. |
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AbstractList | Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose.
Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared.
The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis.
The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation. Background: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. Methods: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. Results: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. Conclusions: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation. KCI Citation Count: 1 |
Author | Yi, Jongyoun Cho, Young-Uk Jo, Su Yeon Jang, Seongsoo Kim, In-Suk Park, Chan-Jeoung Park, Sang Hyuk Kim, Hyung-Hoi Chang, Chulhun L. Lee, Eun Yup Chi, Hyun-Sook |
AuthorAffiliation | 4 Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 1 Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea 3 Biomedical Research Institute, Pusan National University Hospital, Busan, Korea 2 Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea |
AuthorAffiliation_xml | – name: 1 Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea – name: 2 Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea – name: 4 Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea – name: 3 Biomedical Research Institute, Pusan National University Hospital, Busan, Korea |
Author_xml | – sequence: 1 givenname: Su Yeon surname: Jo fullname: Jo, Su Yeon organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea – sequence: 2 givenname: Sang Hyuk surname: Park fullname: Park, Sang Hyuk organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea – sequence: 3 givenname: In-Suk surname: Kim fullname: Kim, In-Suk organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea – sequence: 4 givenname: Jongyoun surname: Yi fullname: Yi, Jongyoun organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea – sequence: 5 givenname: Hyung-Hoi surname: Kim fullname: Kim, Hyung-Hoi organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea – sequence: 6 givenname: Chulhun L. surname: Chang fullname: Chang, Chulhun L. organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea – sequence: 7 givenname: Eun Yup surname: Lee fullname: Lee, Eun Yup organization: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea – sequence: 8 givenname: Young-Uk surname: Cho fullname: Cho, Young-Uk organization: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea – sequence: 9 givenname: Seongsoo surname: Jang fullname: Jang, Seongsoo organization: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea – sequence: 10 givenname: Chan-Jeoung surname: Park fullname: Park, Chan-Jeoung organization: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea – sequence: 11 givenname: Hyun-Sook surname: Chi fullname: Chi, Hyun-Sook organization: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea |
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CitedBy_id | crossref_primary_10_3892_ijmm_2019_4323 crossref_primary_10_1002_jcb_25971 crossref_primary_10_1016_j_heliyon_2017_e00277 crossref_primary_10_1098_rsif_2020_0091 crossref_primary_10_1080_16078454_2021_1990503 crossref_primary_10_3390_medicina58020264 |
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Snippet | Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated... Background: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We... |
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SubjectTerms | Antineoplastic Agents - therapeutic use Bone Marrow - metabolism Bone Marrow - pathology Cytarabine - therapeutic use Daunorubicin fms-Like Tyrosine Kinase 3 - genetics Humans Karyotype Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Mutation Nuclear Proteins - genetics Nuclear Proteins - metabolism Original Real-Time Polymerase Chain Reaction Recurrence Remission Induction Retrospective Studies Sequence Analysis, DNA 병리학 |
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Title | Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A |
URI | https://www.ncbi.nlm.nih.gov/pubmed/27374703 https://pubmed.ncbi.nlm.nih.gov/PMC4940481 https://www.annlabmed.org/journal/download_pdf.php?doi=10.3343/alm.2016.36.5.399 https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002139271 |
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ispartofPNX | Annals of Laboratory Medicine, 2016, 36(5), , pp.399-404 |
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