Biology subjects

Parenti, S.

Publications and source records attributed to Parenti, S..

4 recordsLinked to original sources

bioRxiv2026

Therapy-Induced Clonal Selection as a Driver of Response to JAK Inhibitors in Myelofibrosis

Myelofibrosis (MF) originates from the stepwise acquisition of somatic mutations in Hematopoietic Stem and Progenitor Cells (HSPCs). Alongside driver events triggering JAK-STAT pathway hyperactivation, several additional mutations, usually affecting the epigenetic machinery, contribute defining therapeutic response. Specifically, JAK-inhibition (JAKi) relieves MF symptoms but rarely eradicates the neoplastic clone. To elucidate clonal dynamics associated with JAKi, we conducted a longitudinal single-cell proteogenomic study on 6 responders and 6 non-responders MF patients. Mutational analysis revealed that the mutation acquisition order determines JAKi sensitivity. Indeed, driver-only clones are highly sensitive to JAKi, while co-mutated clones persist after treatment. JAKi response is mainly limited to the differentiated myeloid compartment, while mutant HSPCs are often maintained in JAKi-responders. Co-mutated clones may evade JAKi and outcompete other neoplastic cell populations, thus contributing to disease persistence.

cancer biology↗

bioRxiv2020

Mutated clones driving leukemic transformation are already detectable at the single cell level in CD34-positive cells in the chronic phase of primary myelofibrosis

Disease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decision, we studied single cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF) patient who progressed to acute myeloid Leukemia (AML) while receiving Ruxolitinib. Single cell genomics allowed the reconstruction of clonal hierarchy and demonstrated that TET2 was the first mutated gene while FLT3 was the last one. Disease evolution was accompanied by increased clonal heterogeneity and mutational rate, but clones carrying TP53 and FLT3 mutations were already present in chronic phase. Single cell transcriptomics unraveled repression of interferon signaling suggesting an immunosuppressive effect exerted by Ruxolitinib. Moreover, AML transformation was associated with a differentiative block and immune escape. These results suggest that single cell analysis can unmask tumor heterogeneity and provide meaningful insights about PMF progression that might guide personalized therapy.

cancer biology↗

bioRxiv2020

Neuropeptidome regulation after baculovirus infection. A focus on proctolin and its relevance in locomotion and digestion

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues. Some behavioral and physiological changes in lepidopteran larvae have been described following a baculovirus infection and those changes could be connected with alterations in the hosts central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein-like molecules functioning as neurohormones, neurotransmitters or neuromodulators. These peptides are involved in regulating animal physiology and behaviour and could also be targeted by baculoviruses in order to achieve host behavioural manipulations leading to increased viral fitness. In this study, we have investigated the effect of a Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) infection on the neuropeptidome gene expression of Spodoptera exigua larval heads and brains. Expression of the gene encoding the neuropeptide proctolin was severely downregulated following infection and was chosen for further analysis. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) overexpressing the S. exigua proctolin gene was generated and used in bioassays using S. exigua larvae to study its influence on the viral infection. AcMNPV-proctolin infected larvae showed less locomotion activity and suffered a loss of weight compared to larvae infected with wild type AcMNPV or mock-infected larvae. These results provide additional information on the role of proctolin during a baculovirus infection, and offers a novel hypothesis for the molecular bases for the behavioral changes associated with a baculovirus infection.

genetics↗

bioRxiv2019

Identification of new viruses specific to the honey bee mite Varroa destructor

Large-scale colony losses among managed Western honey bees have become a serious threat to the beekeeping industry in the last decade. There are multiple factors contributing to these losses but the impact of Varroa destructor parasitism is by far the most important, along with the contribution of some pathogenic viruses vectored by the mite. So far, more than 20 viruses have been identified infecting the honey bee, most of them RNA viruses. They may be maintained either as covert infections or causing severe symptomatic infections, compromising the viability of the colony. In silico analysis of available transcriptomic data obtained from mites collected in the USA and Europe as well as additional investigation with new samples collected locally allowed the description of three novel RNA viruses. Our results showed that these viruses were widespread among samples and that they were present in the mites and in the bees but with differences in the relative abundance and prevalence. However, we have obtained strong evidence showing that these three viruses were able to replicate in the mite, but not in the bee, suggesting that they are selectively infecting the mite. To our knowledge, this is the first demonstration of Varroa-specific viruses, which open the door to future applications that might help controlling the mite through biological control approaches.

microbiology↗