ArticleCell research2019
Vulnerabilities in mIDH2 AML confer sensitivity to APL-like targeted combination therapy.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed.
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.Cold Spring Harbor perspectives in medicine · 2024Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Reciprocal antagonism of PIN1-APC/CNature communications · 2024Article
- A machine learning model identifies M3-like subtype in AML based on PML/RARα targets.iScience · 2024Article
- Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies.Genome biology · 2023Article
- The transcription factor HIF2α partakes in the differentiation block of acute myeloid leukemia.EMBO molecular medicine · 2023Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- Update on Small Molecule Targeted Therapies for Acute Myeloid Leukemia.Current treatment options in oncology · 2023Review
- Targeting metabolic vulnerabilities to overcome resistance to therapy in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Article
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- A Pin1/PML/P53 axis activated by retinoic acid inHaematologica · 2021Article
- Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy.Cell · 2021Article
- Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia: Emerging Options and Pending Questions.HemaSphere · 2021Article
- Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia.The Journal of experimental medicine · 2021Article
- Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model.Haematologica · 2021Article
- Endogenous and combination retinoids are active in myelomonocytic leukemias.Haematologica · 2021Article
- Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias.Cancers · 2020Review
- Review
Corrections and comments
- Commented on by
Authors and funding
22 authors.
Funding
Abstract
Although targeted therapies have proven effective and even curative in human leukaemia, resistance often ensues. IDH enzymes are mutated in ~20% of human AML, with targeted therapies under clinical evaluation. We here characterize leukaemia evolution from mutant IDH2 (mIDH2)-dependence to independence identifying key targetable vulnerabilities of mIDH2 leukaemia that are retained during evolution and progression from early to late stages. Mechanistically, we find that mIDH2 leukaemia are metastable and vulnerable at two distinct levels. On the one hand, they are characterized by oxidative and genotoxic stress, in spite of increased 1-carbon metabolism and glutathione levels. On the other hand, mIDH2 leukaemia display inhibition of LSD1 and a resulting transcriptional signature of all-trans retinoic acid (ATRA) sensitization, in spite of a state of suppressed ATRA signalling due to increased levels of PIN1. We further identify GSH/ROS and PIN1/LSD1 as critical nodes for leukaemia maintenance and the combination of ATRA and arsenic trioxide (ATO) as a key therapeutic modality to target these vulnerabilities. Strikingly, we demonstrate that the combination of ATRA and ATO proves to be a powerfully synergistic and effective therapy in a number of mouse and human mIDH1/2 leukemic models. Thus, our findings pave the way towards the treatment of a sizable fraction of human AMLs through targeted APL-like combinatorial therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.