ArticleJCI insight2017
Upregulated heme biosynthesis, an exploitable vulnerability in MYCN-driven leukemogenesis.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 52 citations in OpenAlex.
- HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis.Science advances · 2026Article
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.Science advances · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.bioRxiv : the preprint server for biology · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- Xanthocillin X Dimethyl Ether Exhibits Anti-Proliferative Effect on Triple-Negative Breast Cancer by Depletion of Mitochondrial Heme.Marine drugs · 2025Article
- Deep profiling of gene expression across 18 human cancers.Nature biomedical engineering · 2025Article
- Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.Blood · 2025Article
- Article
- Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.Science advances · 2025Article
- A deep profile of gene expression across 18 human cancers.bioRxiv : the preprint server for biology · 2024Article
- The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.Cancer research · 2024Article
- Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- N-MYC regulates cell survival via eIF4G1 in inv(16) acute myeloid leukemia.Science advances · 2024Article
- Gut microbiota derived metabolite trimethylamine N-oxide influences prostate cancer progression via the p38/HMOX1 pathway.Frontiers in pharmacology · 2024Article
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- A PPIX-binding probe facilitates discovery of PPIX-induced cell death modulation by peroxiredoxin.Communications biology · 2023Article
- Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Heme: The Lord of the Iron Ring.Antioxidants (Basel, Switzerland) · 2023Review
- Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The increased heme biosynthesis long observed in leukemia was previously of unknown significance. Heme, synthesized from porphyrin precursors, plays a central role in oxygen metabolism and mitochondrial function, yet little is known about its role in leukemogenesis. Here, we show increased expression of heme biosynthetic genes, including UROD, only in pediatric AML samples that have high MYCN expression. High expression of both UROD and MYCN predicts poor overall survival and unfavorable outcomes in adult AML. Murine leukemic progenitors derived from hematopoietic progenitor cells (HPCs) overexpressing a MYCN cDNA (MYCN-HPCs) require heme/porphyrin biosynthesis, accompanied by increased oxygen consumption, to fully engage in self-renewal and oncogenic transformation. Blocking heme biosynthesis reduced mitochondrial oxygen consumption and markedly suppressed self-renewal. Leukemic progenitors rely on balanced production of heme and heme intermediates, the porphyrins. Porphyrin homeostasis is required because absence of the porphyrin exporter, ABCG2, increased death of leukemic progenitors in vitro and prolonged the survival of mice transplanted with Abcg2-KO MYCN-HPCs. Pediatric AML patients with elevated MYCN mRNA display strong activation of TP53 target genes. Abcg2-KO MYCN-HPCs were rescued from porphyrin toxicity by p53 loss. This vulnerability was exploited to show that treatment with a porphyrin precursor, coupled with the absence of ABCG2, blocked MYCN-driven leukemogenesis in vivo, thereby demonstrating that porphyrin homeostasis is a pathway crucial to MYCN leukemogenesis.
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.