San Raffaele Bio-medical Park Foundation, Rome, Italy.
Published: May 2007
AI Article Synopsis
Article Abstract
Alteration of lineage-specific transcriptional programs for hematopoiesis causes differentiation block and promotes leukemia development. Here, we show that AML1/ETO, the most common translocation fusion product in acute myeloid leukemia (AML), counteracts the activity of retinoic acid (RA), a transcriptional regulator of myelopoiesis. AML1/ETO participates in a protein complex with the RA receptor alpha (RARalpha) at RA regulatory regions on RARbeta2, which is a key RA target gene mediating RA activity/resistance in cells. At these sites, AML1/ETO recruits histone deacetylase, DNA methyltransferase, and DNA-methyl-CpG binding activities that promote a repressed chromatin conformation. The link among AML1/ETO, heterochromatic RARbeta2 repression, RA resistance, and myeloid differentiation block is indicated by the ability of either siRNA-AML1/ETO or the DNA methylation inhibitor 5-azacytidine to revert these epigenetic alterations and to restore RA differentiation response in AML1/ETO blasts. Finally, RARbeta2 is commonly silenced by hypermethylation in primary AML blasts but not in normal hematopoietic precursors, thus suggesting a role for the epigenetic repression of the RA signaling pathway in myeloid leukemogenesis.
CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention.
Cardiac development is a complex and intricate process involving numerous molecular signals and pathways. Researchers have explored cardiac development through a long journey, starting with early studies observing morphological changes and progressing to the exploration of molecular mechanisms using various molecular biology methods. Currently, advancements in stem cell technology and sequencing technology, such as the generation of human pluripotent stem cells and cardiac organoids, multi-omics sequencing, and artificial intelligence (AI) technology, have enabled researchers to understand the molecular mechanisms of cardiac development better.
Aims: Acute promyelocytic leukemia (APL) progresses quickly and often leads to early hemorrhagic death. Treatment with all-trans retinoic acid (ATRA) promotes differentiation of APL cells and clinical remission, making APL a potentially curable malignancy. Understanding how ATRA works may lead to new treatments for other types of leukemia.
Purpose: Ambient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All- retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retino-scleral signaling cascade underlying myopic eye growth.
Background And Purpose: Cellulite is caused by changes in the metabolism of the fatty tissue beneath the skin. Methylxanthines and retinoids are commonly added to the different anticellulite products. However, their topical permeation into the dermis is limited.
