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Retinoids in leukemia and cellular processes
Research Guide
What is Retinoids in leukemia and cellular processes?
Retinoids in leukemia and cellular processes refer to the biological roles of retinoic acid and related vitamin A derivatives in regulating gene expression through nuclear receptors like RXR, inducing differentiation in acute promyelocytic leukemia, and influencing processes such as cell senescence, lipid peroxidation, and embryonic development.
This field encompasses 61,838 works examining retinoic acid's interactions with nuclear receptors such as RXR in gene expression regulation and differentiation therapy for acute promyelocytic leukemia. Key studies detail RXR heterodimers and orphan receptors, as shown in 'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans. Research also connects retinoids to cellular senescence mechanisms involving p53 and p16INK4a, per 'Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a' (1997) by Serrano et al.
Topic Hierarchy
Research Sub-Topics
Retinoic Acid in Acute Promyelocytic Leukemia
This sub-topic investigates all-trans retinoic acid (ATRA) therapy for APL, including PML-RARα degradation and differentiation induction. Researchers study resistance mechanisms and combination therapies.
RAR-RXR Heterodimer Signaling
This sub-topic explores the molecular mechanisms of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers in gene transcription regulation. Researchers analyze co-regulators, ligand specificity, and chromatin interactions.
Retinoic Acid in Embryonic Development
This sub-topic examines retinoic acid gradients and signaling in pattern formation, limb development, and organogenesis. Researchers use genetic models to study Hox gene regulation and teratogenic effects.
Arsenic Trioxide in APL Therapy
This sub-topic focuses on arsenic trioxide's mechanism in APL, including PML sumoylation and autophagy induction, often combined with ATRA. Researchers optimize dosing and explore non-APL applications.
Retinoic Acid Gene Expression Regulation
This sub-topic studies retinoic acid-responsive elements (RAREs) and transcriptional networks controlled by RA signaling. Researchers employ ChIP-seq and CRISPR to map targets in differentiation and homeostasis.
Why It Matters
Retinoids drive differentiation therapy in acute promyelocytic leukemia through retinoic acid's action on nuclear receptors like RXR, often combined with arsenic trioxide. 'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans (3168 citations) establishes RXR's role in heterodimer formation for gene regulation, directly relevant to leukemia treatment pathways. Clinical trials in 'Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease' (1996) by Omenn et al. (3606 citations) showed that beta carotene and vitamin A supplementation increased lung cancer incidence and mortality risk in 18,000+ smokers and asbestos workers after four years, highlighting retinoid dosing risks in cancer contexts. These findings inform precise therapeutic applications in leukemia while cautioning against broad supplementation in high-risk groups.
Reading Guide
Where to Start
'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans, as it provides the foundational overview of RXR's central role in retinoid signaling, essential for understanding leukemia applications.
Key Papers Explained
'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans (3168 citations) lays the basis for RXR heterodimer function, which 'Cloning of a novel receptor expressed in rat prostate and ovary' (1996) by Kuiper et al. (4789 citations) extends by identifying a new RXR-like receptor. 'Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a' (1997) by Serrano et al. (4993 citations) connects these pathways to senescence, while 'Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal' (2014) by Ayala et al. (5826 citations) details downstream oxidative signaling relevant to retinoid-induced stress in leukemia.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Field focuses on refining differentiation therapy combinations with arsenic trioxide for acute promyelocytic leukemia resistance; no recent preprints available, but core mechanisms from top papers like Mangelsdorf and Evans (1995) remain central to ongoing nuclear receptor studies.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Lipid Peroxidation: Production, Metabolism, and Signaling Mech... | 2014 | Oxidative Medicine and... | 5.8K | ✓ |
| 2 | Oncogenic ras Provokes Premature Cell Senescence Associated wi... | 1997 | Cell | 5.0K | ✓ |
| 3 | The retinoblastoma protein and cell cycle control | 1995 | Cell | 4.9K | ✓ |
| 4 | Cloning of a novel receptor expressed in rat prostate and ovary. | 1996 | Proceedings of the Nat... | 4.8K | ✓ |
| 5 | Comparison of the Ligand Binding Specificity and Transcript Ti... | 1997 | Endocrinology | 4.4K | ✓ |
| 6 | Cellular senescence: when bad things happen to good cells | 2007 | Nature Reviews Molecul... | 4.2K | ✕ |
| 7 | Effects of a Combination of Beta Carotene and Vitamin A on Lun... | 1996 | New England Journal of... | 3.6K | ✓ |
| 8 | A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-mo... | 1994 | Journal of Biological ... | 3.2K | ✓ |
| 9 | The RXR heterodimers and orphan receptors | 1995 | Cell | 3.2K | ✓ |
| 10 | Cloning of adiponectin receptors that mediate antidiabetic met... | 2003 | Nature | 3.1K | ✕ |
Frequently Asked Questions
What role does retinoic acid play in acute promyelocytic leukemia?
Retinoic acid induces differentiation of leukemic cells via nuclear receptors like RXR in acute promyelocytic leukemia. It regulates gene expression to promote maturation of promyelocytes. Arsenic trioxide often complements this therapy targeting PML nuclear bodies.
How do RXR receptors function in retinoid signaling?
'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans details RXR forming heterodimers with other nuclear receptors to regulate gene transcription. RXR binds retinoic acid and influences processes like cell differentiation. This mechanism underlies retinoid effects in leukemia and development.
What is the link between retinoids and cellular senescence?
'Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a' (1997) by Serrano et al. (4993 citations) shows ras-induced senescence involves p53 and p16INK4a accumulation, pathways modulated by retinoid signaling. Retinoids influence senescence via nuclear receptor-mediated gene regulation. This connects to leukemia differentiation therapy.
Why was vitamin A supplementation harmful in some cancer trials?
'Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease' (1996) by Omenn et al. reports increased lung cancer incidence and death risk after four years of beta carotene plus vitamin A in smokers and asbestos-exposed workers. The trial involved two randomized groups totaling over 18,000 participants. Results underscore retinoid risks in specific populations.
What are PML nuclear bodies in retinoid-leukemia contexts?
PML nuclear bodies are subnuclear structures targeted by retinoic acid and arsenic trioxide in acute promyelocytic leukemia therapy. Retinoids disrupt PML-RARα fusion proteins localized there. This action restores normal differentiation.
How do retinoids regulate gene expression?
Retinoids bind RXR and other nuclear receptors to form heterodimers that control transcription. 'The RXR heterodimers and orphan receptors' (1995) by Mangelsdorf and Evans (3168 citations) describes this heterodimerization. Processes like vitamin A metabolism and embryonic development depend on it.
Open Research Questions
- ? How do RXR heterodimers specifically interact with PML-RARα fusions to enable differentiation in acute promyelocytic leukemia?
- ? What precise mechanisms link retinoic acid signaling to p53/p16INK4a-mediated senescence in leukemic cells?
- ? Can optimized retinoid-arsenic trioxide combinations overcome resistance in relapsed acute promyelocytic leukemia cases?
- ? How does lipid peroxidation from retinoid metabolism, as in 'Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal' (2014) by Ayala et al., influence leukemia cell fate?
- ? What role do novel RXR-like receptors, per 'Cloning of a novel receptor expressed in rat prostate and ovary' (1996) by Kuiper et al., play in non-hematopoietic retinoid responses relevant to leukemia?
Recent Trends
The field holds steady at 61,838 works with no reported 5-year growth data; high citation classics like 'Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal' by Ayala et al. (5826 citations) continue dominating, linking retinoid metabolism to oxidative signaling.
2014No recent preprints or news in last 12 months indicate stable research emphasis on established RXR pathways and leukemia therapy.
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