| Mutations of the epigenetics modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia. | |
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MedLine Citation:
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PMID: 23135354 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at diagnosis and relapse of 34 adult AML patients. 5 acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as FLT3 and RAS mutations. The disappeared mutations at relapse were 3 of 11 FLT3-ITD (27.3%), 3 of 3 FLT3-TKD (100%), 3 of 13 NPM1 (23.1%) and 2 of 5 C/EBPá (40%) mutations. However, epigenetics modifying genes (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics modifying gene mutations (P<0.001). Our results suggest that epigenetics modifying gene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.Leukemia accepted article preview online, 8 November 2012; doi:10.1038/leu.2012.317. |
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Authors:
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S Wakita; H Yamaguchi; I Omori; K Terada; T Ueda; E Manabe; S Kurosawa; S Iida; T Ibaraki; Y Sato; T Todoroki; T Hirakawa; T Ryotokuji; K Arai; T Kitano; Y M; F Kosaka; K Dan; K Inokuchi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-08 |
Journal Detail:
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Title: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K Volume: - ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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