ArticleNature cancer2022
IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- IKZF1Leukemia · 2026Article
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Outcomes of relapsed or refractory acute myeloid leukemia after menin inhibition failure.Blood advances · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Exosome-derived Menin from cancer-associated fibroblasts promotes gastric cancer progression by activating the HSPA6/JNK/JunD pathway and inducing EMT.Journal of translational medicine · 2025Article
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Recent advances in drug delivery and treatment strategies for acute myeloid leukemia.International journal of pharmaceutics · 2025Review
- Image-based drug screening combined with molecular profiling identifies signatures and drivers of therapy resistance in pediatric AML.Cell reports. Medicine · 2025Article
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review.Diseases (Basel, Switzerland) · 2025Review
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- The IKZF1 N159S mutation is associated with poor outcome and a distinct molecular profile in adult patients with AML.British journal of haematology · 2025Article
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
- Article
- Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead.Journal of hematology & oncology · 2024Review
- Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.Cancer medicine · 2024Review
- Review
- Menin in Cancer.Genes · 2024Review
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25 authors at 8 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation. Furthermore, IKAROS displays an unexpected functional cooperativity and extensive chromatin co-occupancy with mixed lineage leukemia (MLL)1-MENIN and the regulator MEIS1 and an extensive hematopoietic transcriptional complex involving homeobox (HOX)A10, MEIS1 and IKAROS. This dependency could be therapeutically exploited by inducing IKAROS protein degradation with immunomodulatory imide drugs (IMiDs). Finally, we demonstrate that combined IKAROS degradation and MENIN inhibition effectively disrupts leukemogenic transcriptional networks, resulting in synergistic killing of leukemia cells and providing a paradigm for improved drug targeting of transcription and an opportunity for rapid clinical translation.
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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.