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  1. Article ; Online: In vitro interactions between Bradyrhizobium spp. and Tuber magnatum mycelium.

    Graziosi, Simone / Puliga, Federico / Iotti, Mirco / Amicucci, Antonella / Zambonelli, Alessandra

    Environmental microbiology reports

    2024  Volume 16, Issue 3, Page(s) e13271

    Abstract: Tuber magnatum is the most expensive truffle, but its large-scale cultivation is still a challenge compared to other valuable Tuber species. T. magnatum mycelium has never been grown profitably until now, which has led to difficulties to studying it in ... ...

    Abstract Tuber magnatum is the most expensive truffle, but its large-scale cultivation is still a challenge compared to other valuable Tuber species. T. magnatum mycelium has never been grown profitably until now, which has led to difficulties to studying it in vitro. This study describes beneficial interactions between T. magnatum mycelium and never before described bradyrhizobia, which allows the in vitro growth of T. magnatum mycelium. Three T. magnatum strains were co-isolated on modified Woody Plant Medium (mWPM) with aerobic bacteria and characterised through microscopic observations. The difficulties of growing alone both partners, bacteria and T. magnatum mycelium, on mWPM demonstrated the reciprocal dependency. Three bacterial isolates for each T. magnatum strain were obtained and molecularly characterised by sequencing the 16S rRNA, glnII, recA and nifH genes. Phylogenetic analyses showed that all nine bacterial strains were distributed among five subclades included in a new monophyletic lineage belonging to the Bradyrhizobium genus within the Bradyrhizobium jicamae supergroup. The nifH genes were detected in all bacterial isolates, suggesting nitrogen-fixing capacities. This is the first report of consistent T. magnatum mycelium growth in vitro conditions. It has important implications for the development of new technologies in white truffle cultivation and for further studies on T. magnatum biology and genetics.
    MeSH term(s) Bradyrhizobium/genetics ; Bradyrhizobium/classification ; Bradyrhizobium/isolation & purification ; Bradyrhizobium/physiology ; Bradyrhizobium/growth & development ; Bradyrhizobium/metabolism ; Mycelium/growth & development ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Nitrogen Fixation ; DNA, Bacterial/genetics ; Symbiosis
    Chemical Substances RNA, Ribosomal, 16S ; DNA, Bacterial
    Language English
    Publishing date 2024-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1758-2229
    ISSN (online) 1758-2229
    DOI 10.1111/1758-2229.13271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Unveiling the signaling network of FLT3-ITD AML improves drug sensitivity prediction.

    Latini, Sara / Venafra, Veronica / Massacci, Giorgia / Bica, Valeria / Graziosi, Simone / Pugliese, Giusj Monia / Iannuccelli, Marta / Frioni, Filippo / Minnella, Gessica / Marra, John Donald / Chiusolo, Patrizia / Pepe, Gerardo / Helmer Citterich, Manuela / Mougiakakos, Dimitros / Böttcher, Martin / Fischer, Thomas / Perfetto, Livia / Sacco, Francesca

    eLife

    2024  Volume 12

    Abstract: Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical ... ...

    Abstract Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical internal tandem duplications (ITDs) in the tyrosine kinase domain of the FLT3 gene. To address this unmet medical need, here we develop a systems-based strategy that integrates multiparametric analysis of crucial signaling pathways, and patient-specific genomic and transcriptomic data with a prior knowledge signaling network using a Boolean-based formalism. By this approach, we derive personalized predictive models describing the signaling landscape of AML FLT3-ITD positive cell lines and patients. These models enable us to derive mechanistic insight into drug resistance mechanisms and suggest novel opportunities for combinatorial treatments. Interestingly, our analysis reveals that the JNK kinase pathway plays a crucial role in the tyrosine kinase inhibitor response of FLT3-ITD cells through cell cycle regulation. Finally, our work shows that patient-specific logic models have the potential to inform precision medicine approaches.
    MeSH term(s) Humans ; Signal Transduction ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; MAP Kinase Signaling System ; Cell Line ; Drug Resistance ; fms-Like Tyrosine Kinase 3/genetics
    Chemical Substances FLT3 protein, human (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1)
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.90532
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Impact of FLT3-ITD location on cytarabine sensitivity in AML: a network-based approach.

    Pugliese, Giusj Monia / Venafra, Veronica / Bica, Valeria / Massacci, Giorgia / Latini, Sara / Graziosi, Simone / Fischer, Thomas / Mougiakakos, Dimitrios / Boettcher, Martin / Perfetto, Livia / Sacco, Francesca

    Leukemia

    2023  Volume 37, Issue 5, Page(s) 1151–1155

    MeSH term(s) Humans ; Cytarabine/pharmacology ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Cell Line, Tumor ; fms-Like Tyrosine Kinase 3/genetics ; Mutation
    Chemical Substances Cytarabine (04079A1RDZ) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; FLT3 protein, human (EC 2.7.10.1)
    Language English
    Publishing date 2023-03-25
    Publishing country England
    Document type Research Support, Non-U.S. Gov't ; Letter
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-023-01881-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A key role of the WEE1-CDK1 axis in mediating TKI-therapy resistance in FLT3-ITD positive acute myeloid leukemia patients.

    Massacci, Giorgia / Venafra, Veronica / Latini, Sara / Bica, Valeria / Pugliese, Giusj Monia / Graziosi, Simone / Klingelhuber, Felix / Krahmer, Natalie / Fischer, Thomas / Mougiakakos, Dimitrios / Boettcher, Martin / Perfetto, Livia / Sacco, Francesca

    Leukemia

    2022  Volume 37, Issue 2, Page(s) 288–297

    Abstract: The insertion site of the internal tandem duplications (ITDs) in the FLT3 gene affects the sensitivity to tyrosine kinase inhibitors (TKIs) therapy in acute myeloid leukemia (AML). Patients with the ITD in the tyrosine kinase domain lack effective ... ...

    Abstract The insertion site of the internal tandem duplications (ITDs) in the FLT3 gene affects the sensitivity to tyrosine kinase inhibitors (TKIs) therapy in acute myeloid leukemia (AML). Patients with the ITD in the tyrosine kinase domain lack effective therapeutic options. Here, to identify genotype-driven strategies increasing the TKI therapy efficacy, we developed SignalingProfiler, a strategy supporting the integration of high-sensitive mass spectrometry-based (phospho)proteomics, RNA sequencing datasets with literature-derived signaling networks. The approach generated FLT3-ITD genotype-specific predictive models and revealed a conserved role of the WEE1-CDK1 axis in TKIs resistance. Remarkably, pharmacological inhibition of the WEE1 kinase synergizes and strengthens the pro-apoptotic effect of TKIs therapy in cell lines and patient-derived primary blasts. Finally, we propose a new molecular mechanism of TKIs resistance in AML and suggest the combination of WEE1 inhibitor and TKI as a therapeutic option to improve patients clinical outcome.
    MeSH term(s) Humans ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Cell Line ; Signal Transduction ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; fms-Like Tyrosine Kinase 3/genetics ; fms-Like Tyrosine Kinase 3/metabolism ; Mutation ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; CDC2 Protein Kinase/genetics ; CDC2 Protein Kinase/metabolism ; CDC2 Protein Kinase/pharmacology
    Chemical Substances Protein Kinase Inhibitors ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; FLT3 protein, human (EC 2.7.10.1) ; WEE1 protein, human (EC 2.7.10.2) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Cell Cycle Proteins ; CDK1 protein, human (EC 2.7.11.22) ; CDC2 Protein Kinase (EC 2.7.11.22)
    Language English
    Publishing date 2022-12-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-022-01785-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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