Evidence map›Paper›PMID 23135354›Full record

ArticleLeukemia2013

Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.

S Wakita, H Yamaguchi, I Omori, K Terada, T Ueda, E Manabe, S Kurosawa, S Iida, T Ibaraki, Y Sato and 9 more

Abstract read
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In one paragraph

Article in Leukemia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Observational
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  10. Article
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  12. DNA methyltransferases in hematological malignancies.Journal of genetics and genomics = Yi chuan xue bao · 2020
    Review
  13. Article
  14. Observational
  15. The sensitivity of theLeukemia research reports · 2020
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 1 institution in 1 country.

S WakitaDepartment of Internal Medicine, Division of Hematology, Nippon Medical School, Tokyo, Japan.
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 Mitamura
F Kosaka
K Dan
K Inokuchi
Nippon Medical School · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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. Five 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 Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (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 indicate that epigenetics-modifying gene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.

Indexed as

MutationDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEpigenomicsfms-Like Tyrosine Kinase 3HumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteNucleophosminProto-Oncogene ProteinsRecurrenceDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanFLT3 protein, humanfms-Like Tyrosine Kinase 3IDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseNpm1 protein, ratNucleophosminProto-Oncogene ProteinsTET2 protein, human

Identifiers

PMID23135354
OpenAlexW1966379304

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.