RARA (Retinoic Acid Receptor Alpha)

Conversely, the N-to-C synthesis method proceeded efficiently without cysteine protection, thereby simplifying the workflow and reducing the number of purification steps. This research presents a reliable and accessible method for the complete chemical synthesis of RNF4, addressing significant challenges in synthesizing large proteins and opening up new opportunities for future biological research.

Compared with non-APL-AML patients, APL patients (PML-RARα (S-type) and PML-RARα (L-type)) exhibit unique immunophenotypic changes. The expression frequencies of CD56, CD2, CD34, and CD200 in leukemia cells are significantly correlated with the OS of APL patients, and the high expression of these indicators before treatment may be an adverse prognostic factor for APL patients.

(3) Clinical evidence confirms that ATRA combined with arsenic trioxide or epigenetic modulators achieves high remission rates in APL and selected AML subtypes...(4) ATRA-based combination therapies represent a promising strategy to extend differentiation therapy beyond APL. This review, authored solely by the investigator, highlights molecular targets and potential enhancers warranting further clinical evaluation in AML.

Notably, demethylation therapy induced sustained complete remission in patients with refractory recurrent APL during experimental treatment. Our findings underscore the critical role of ALDH1A3 in leukemogenesis and highlight its potential as a therapeutic target in APL.

This work provides a robust tool for early APL diagnosis. The proposed triple-amplification strategy and the rational design of the ECL-RET platform offer a generalizable and versatile sensing paradigm, which can be readily adapted for the ultrasensitive detection of a wide range of other disease-related nucleic acid biomarkers and infectious pathogens.

It is possible that ATRA induces conformational changes and/or promotes nuclear translocation of RARα, which in turn reduces its interaction with TACC1v25 and modulates the downstream transcriptional effects. This may provide new ideas for treating HNSCCs.

Fenofibrate effectively counteracted these effects by activating PPARα, thereby competitively inhibiting RARα binding to RXRα and restoring lipid homeostasis. This study reveals a novel mechanism underlying ATRA-induced hyperlipidemia and hepatic lipid accumulation, which offers a theoretical foundation for the clinical use of fenofibrate in managing ATRA-induced hyperlipidemia and hepatic steatosis.

P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Our findings expand the understanding of ERα mutations beyond known hotspots, identifying L370F as a novel mutation contributing to ET resistance and further indicate the necessity to characterize all the less-studied ERα variants found in MBC. Furthermore, we demonstrate that ATRA selectively targets MBC cells harboring L370F and Y537S mutations, suggesting its potential as a mutation-specific therapeutic agent. These results support further investigation of ATRA in clinical settings to improve treatment strategies for ERα-mutant MBC.

Furthermore, the article explores the importance of the immune system in acute promyelocytic leukemia treatment response and the impact of all-trans retinoic acid/arsenic trioxide therapy on the proteome and metabolome. By synthesizing existing research findings, this review aims to discuss how proteomic and metabolomic data elucidate the pathological mechanisms and therapeutic targets of acute promyelocytic leukemia, providing a theoretical basis for future precision medicine and translational research.

Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10-20% of patients develop drug resistance due to mutations in PML-RARα and other factors...Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.

P2, N=153, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027