Collectively, our results suggest that tamibarotene may elicit detrimental effects in patients with EBA by abolishing the recruitment of Tregs into skin. This warrants great caution when using tamibarotene in patients with EBA and possibly other pemphigoid diseases.

Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases.

In addition, it suppressed lysosomal activity by 2.73-fold in MCF7 and 2.52-fold in MDA-MB-468, as demonstrated by lysotracker assays. These findings underscore the potential of Adapalene as a multi-targeted modulator of RARα-PI3K signaling, effectively disrupting autophagy and cancer cell survival mechanisms in luminal and triple-negative breast cancer cells.

The present study, for the first time, uncovered the inhibition effect of bisphenols on RARα signaling via ERα agonism, and highlighted the antagonistic crosstalk between ERα and RARα signaling. The findings provide a novel perspective to understand the complicated endocrine disrupting effects of emerging chemicals with binding affinities for multiple NRs, and emphasize the importance of studying the crosstalk between diverse NR-regulated signaling that is concerned.

The use of tamibarotene-based therapy to target RARα as a novel approach in HR-MDS pts with RARA gene overexpression is not a paradigm which can augment response rates beyond HMA monotherapy. Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted.

A. Sahebkar disagrees with the retraction, the other co-authors remained unresponsive.

CDK9 also promotes degradation of retinoic acid receptor α (RARα) via recruiting the E3 ligase HUWE1. Co-administration of CDK9-PROTAC (GT-02897) with all-trans retinoic acid (ATRA) leads to synergistic attenuation of tumor growth in vitro and in xenograft models, providing a potential translational treatment for complete eradication of CTCL.

The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.

The standard clinical therapies all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce PML/RARα proteolysis, have dramatically improved the prognosis of APL patients...Consistently, the depletion or inhibition of ZDHHC3 could significantly arrest the malignant progression of APL, particularly drug-resistant APL, whereas ZDHHC3 overexpression appeared to have a promoting effect on the malignant progression of APL. Thus, our study not only reveals palmitoylation as a novel regulatory mechanism that modulates PML/RARα oncogenic activity but also identifies ZDHHC3 as a potential therapeutic target for APL, including drug-resistant APL.

Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.

Finally, a series of experimental validations in primary APL patient samples confirm that PML/RARα forms microspeckles through condensates, recruits BRD4 to coassemble condensates, and co-occupies SEBP regions. Our findings elucidate the biophysical, pathological, and transcriptional dynamics of PML/RARα-assembled microspeckles, underscoring the importance of BRD4 in mediating transcriptional activation that enables PML/RARα to initiate APL.

Secondly, our patient represents, to the best of our knowledge, the first documented example of this rare disease that has been managed with, and shown sensitivity to low-dose cytarabine (LDAC) in combination with venetoclax (Ven). This case demonstrates that although treatment options are extremely limited for patients not eligible for intensive chemotherapy non-intensive options do show increasing promise.