Evidence map›Paper›PMID 26686245›Full record

ArticleLeukemia2016

The combination of FLT3 and DNA methyltransferase inhibition is synergistically cytotoxic to FLT3/ITD acute myeloid leukemia cells.

E Chang, S Ganguly, T Rajkhowa, C D Gocke, M Levis, H Konig

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.8field-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

35 citing papers in PubMed, 57 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Targeting p16Leukemia · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Disease markers · 2021
    Article
  18. Epigenetic Mechanisms in Leukemias and Lymphomas.Cold Spring Harbor perspectives in medicine · 2020
    Review
  19. Overcoming Resistance to FLT3 Inhibitors in the Treatment ofInternational journal of molecular sciences · 2020
    Review
  20. Frontiers in oncology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

E ChangSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
S GangulySidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-2662-8897
T RajkhowaSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
C D GockeDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
M LevisSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
H KonigDivision of Hematology/Oncology, Department of Medicine, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
Johns Hopkins University · USIndiana University Health · US

Funding

University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
NCI NIH HHS P50 CA100632
6 · The paper itself

Abstract

Effective treatment regimens for elderly acute myeloid leukemia (AML) patients harboring internal tandem duplication mutations in the FMS-like tyrosine kinase-3 (FLT3) gene (FLT3/ITD) are lacking and represent a significant unmet need. Recent data on the effects of FLT3 tyrosine kinase inhibitors on FLT3/ITD(+) AML showed promising clinical activity, including in elderly patients. DNA methyltransferase (DNMT) inhibitors such as decitabine (5-aza-2-deoxycytidine, DEC) and 5-azacitidine (AZA) demonstrated clinical benefit in AML, are well tolerated and are associated with minimal increases in FLT3 ligand, which can represent a potential resistance mechanism to FLT3 inhibitors. In addition, both FLT3 and DNMT inhibition are associated with the induction of terminal differentiation of myeloid blasts. Consequently, there is a strong theoretical rationale for combining FLT3 and DNMT inhibition for FLT3/ITD(+) AML. We therefore sought to study the anti-leukemic effects of DEC, AZA and FLT3 inhibitors, either as single agents or in combination, on AML cell lines and primary cells derived from newly diagnosed and relapsed AML patients. Our studies indicate that combined treatment using FLT3 inhibition and hypomethylation confers synergistic anti-leukemic effects, including apoptosis, growth inhibition and differentiation. The simultaneous administration of AZA and FLT3 inhibition appears to be the most efficacious combination in this regard. These drugs may provide a novel therapeutic approach for FLT3/ITD(+) AML, in particular for older patients.

Indexed as

AgedAged, 80 and overAntineoplastic AgentsApoptosisAzacitidineCell DifferentiationCell Line, TumorCell ProliferationDecitabineDNA Modification MethylasesDrug SynergismEnzyme Inhibitorsfms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteTumor Cells, CulturedAntineoplastic AgentsAzacitidineDecitabineDNA Modification MethylasesEnzyme InhibitorsFLT3 protein, humanfms-Like Tyrosine Kinase 3

Identifiers

PMID26686245
PMCPMC5244408
OpenAlexW2219101733

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.