Biology subjects

Cheloni, G.

Publications and source records attributed to Cheloni, G..

4 recordsLinked to original sources

bioRxiv2026

Tumor suppressor-like mutations mark a dosage-constrained dependency in leukemia

Cancer genes are classically categorized as oncogenes or tumor suppressors based on whether gain or loss of function promotes malignancy. Here we show that oncogene-imposed dosage constraints can produce mutations that mimic tumor suppressor loss yet mark essential genes. In acute promyelocytic leukemia (APL), the transcription factor EBF3 gene harbors recurrent heterozygous loss-of-function mutations, a tumor suppressor signature, and is essential for APL survival. We resolve this paradox by showing that while PML::RARA, the fusion oncoprotein defining APL, drives EBF3 expression, excess EBF3 suppresses proliferation. Patient mutations reduce EBF3 activity through heterozygous inactivation, optimizing its expression within a corridor bounded by fitness constraints at both extremes. PML::RARA activates EBF3 via a p300-dependent intronic enhancer, and p300 inhibition exploits this constraint by suppressing EBF3 below the viability threshold. Our findings reveal that oncogenes can impose dosage constraints that drive adaptive mutations conventionally misclassified as tumor suppressor loss, with implications for interpreting cancer genomes.

cancer biology↗

bioRxiv2025

Diclofenac stress responses and biotransformation pathways in the marine diatom Phaeodactylum tricornutum

Effects of organic contaminants (OCs) on phytoplankton physiology were extensively studied in the last years while a knowledge gap exists regarding the ability of phytoplankton to transform OCs. Knowledge about biotransformation pathways in these organisms lag far behind that of other microorganisms. A better understanding of biotransformation pathways would help identify biomarkers of contaminants exposure, improve microalgae-based water remediation strategies and help better assess contaminants persistence and trophic transfer in natural aquatic environments. The present study investigated diclofenac (DCF) physiological effects, transcriptional responses and metabolism in the marine diatom Phaeodactylum tricornutum with the aim of getting an insight on detoxifications pathways. P. tricornutum did not result in significant removal capacity of DCF from the exposure medium. Bioconcentration factors varied depending on the exposure concentration (3.9 and 2.7 for 1.5 mg L-1 and 10 mg L-1 DCF respectively) but remained relatively low. DCF resulted in mild physiological effects on P. tricornutum but gene expression analysis indicated that multiple molecular functions and biological processes were altered by DCF exposure. Transcriptomic analysis suggested increased nutrients and energy requirements possibly associated with the contaminant stress and detoxification metabolism. CYP gene expression was not significantly regulated upon DCF exposure but 4-Hydroxy Diclofenac (OH-DCF), a metabolite generally associated with CYP enzymatic activity, was detected. However, CYP gene expression was not significantly regulated upon DCF exposure. Five additional DCF metabolites with high molecular weight were detected. These metabolites were not previously described in the literature and were suggested to be generated via amino acid (or peptides) conjugation. Gene ontology analysis indicated that amino acid and peptide biosynthetic pathways were regulated upon DCF exposure supporting a possible correlation between organic contaminants detoxification responses and amino acid and protein content in phytoplankton cells. Our findings contribute to highlighting the diversity of biotransformation pathways in phytoplankton and provide mechanistic information about contaminants detoxification.

microbiology↗

bioRxiv2024

A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma

Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.

genomics↗

bioRxiv2020

Morphological plasticity in Chlamydomonas reinhardtii and acclimation to micropollutant stress

Phytoplankton are characterized by a great phenotypic plasticity and amazing morphological variability, both playing a primary role in the acclimation to changing environments. However, there is a knowledge gap concerning the role of algal morphological plasticity in stress responses and acclimation to micropollutants. The present study aims examining the palmelloid colony formation of the green alga Chlamydomonas reinhardtii upon micropollutants exposure. Cells were exposed to four micropollutants (MPs) with different modes of action (copper, cadmium, PFOS and paraquat) for a duration of 72h. Effects of MPs on palmelloid formation, growth and physiological traits (chlorophyll fluorescence, membrane integrity and oxidative stress) were monitored via flow cytometry and fluorescence microscopy. Palmelloid formation was observed upon treatment with the four micropollutants. Number of palmelloid colonies and their size were dependent on MP concentration and exposure duration. Cells reverted to their unicellular lifestyle when colonies were harvested and inoculated in fresh medium indicating that palmelloid formation is a plastic response to micropollutants. No physiological effects of these compounds were observed in cells forming palmelloids and palmelloid colonies accumulated lower Cd concentration than unicellular C. reinhardtii suggesting that colony formation protects the cells form MPs exposure. The results show that colony formation in Chlamydomonas reinhardtii is a stress response strategy activated to face sub-lethal micropollutant concentrations. HIGHLIGHTSO_LISub-lethal concentrations of micropollutants (MPs) induce palmelloid formation in C. reinhardtii C_LIO_LIMorphological changes are not associated to adverse effects on algal cells C_LIO_LIPalmelloid formation is transitory, cells revert to unicellular lifestyle in the absence of MPs C_LIO_LICells within large colonies experience lower Cd exposure than unicellular C. reinhardtii C_LIO_LIPalmelloid formation is a morphological stress response that plays a role in cells acclimation to MPs C_LI

pharmacology and toxicology↗