A5043532640- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Lung Cancer Research Studies
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Cancer, Stress, Anesthesia, and Immune Response
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- Chemical Reactions and Isotopes
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Melanoma and MAPK Pathways
University of Turin
2014-2025
Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
2015-2025
University of Freiburg
2018-2024
Novartis (Switzerland)
2024
University Medical Center Freiburg
2018-2024
German Cancer Research Center
2022
Heidelberg University
2022
University of Tsukuba Hospital
2019
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including large-cell (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, oncogenic activity of ALK stimulates signaling pathways that induce transformation promote tumor growth. search for common activated by across different tumors types, we found hypoxia were significantly enriched ALK-rearranged ALCL NSCLC, as compared with other types T-cell or EGFR- K-RAS-mutated...
Abstract Non–small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine inhibitors (TKI), but treatment successful for only a limited amount time; most patients experience relapse due to development drug resistance. Here, we show that vaccine against induced strong and specific immune response both prophylactically therapeutically impaired growth ALK-positive tumors in mouse models. The was efficacious also...
// Claudia Voena 1, 2, 3, * , Lydia M. Varesio Liye Zhang 4, Matteo Menotti 2 Teresa Poggio Elena Panizza Qi Wang 3 Valerio G. Minero Sharmila Fagoonee 5 Mara Compagno Fiorella Altruda Stefano Monti 4 Roberto Chiarle 1 Department of Molecular Biotechnology and Health Sciences, University Torino, Italy Center for Experimental Research Medical Studies (CERMS), Città della Salute e Scienza, Pathology, Children's Hospital Harvard School, Boston, USA Section Computational Biomedicine, Boston...
Abstract Cancer evolution is a process that still poorly understood because of the lack versatile in vivo longitudinal studies. By generating murine non–small cell lung cancer (NSCLC) orthoallobanks and paired primary lines, we provide detailed description an vivo, time-dependent malignization process. We identify acquisition metastatic dissemination potential, selection co-driver mutations, appearance naturally occurring intratumor heterogeneity, thus recapitulating stochastic nature human...
Abstract Ruxolitinib is a potent JAK1/JAK2 inhibitor, approved for the treatment of primary myelofibrosis (PMF) patients based on concept inhibition oncogenic signaling. However, effect ruxolitinib JAK2-V617F allelic burden modest, suggesting that signaling-driven clone expansion not main mechanism action. We evaluate whether mainly blocks proliferation malignant or exerts its effects also by targeting non-malignant cells. Therefore, we develop two JAK2-V617F-driven myeloproliferative...
Abstract FLT3-ITD is the most predominant mutation in AML being expressed about one-third of patients and associated with a poor prognosis. Efforts to better understand downstream signaling possibly improve therapy response are needed. We have previously described FLT3-ITD-dependent phosphorylation CSF2RB, common receptor beta chain IL-3, IL-5, GM-CSF, therefore examined its significance for oncogenic transformation. discovered that directly binds CSF2RB cell lines blasts isolated from...
The expression of BCL6 in B-cell lymphoma can be deregulated by chromosomal translocations, somatic mutations the promoter regulatory regions, or reduced proteasome-mediated degradation. FBXO11 was recently identified as a ubiquitin ligase that is involved degradation BCL6, and it frequently inactivated other tumors. Here, we show are found 23% patients with Burkitt (BL). impaired degradation, deletion protein completely stabilized levels human BL cell lines. Conditional 1 2 copies gene mice...
The t(1;19) translocation, encoding the oncogenic fusion protein E2A (TCF3)-PBX1, is involved in acute lymphoblastic leukemia (ALL) and associated with a pre-B-cell receptor (preBCR+) phenotype. Relapse patients E2A-PBX1+ ALL frequently occurs central nervous system (CNS). Therefore, there medical need for identification of CNS active regimens treatment E2A-PBX1+/preBCR+ ALL. Using unbiased short hairpin RNA (shRNA) library screening approaches, we identified Bruton tyrosine kinase (BTK) as...
Inherited bone marrow failure syndromes (IBMFSs) are a heterogeneous group of disorders characterized by defective hematopoiesis, impaired stem cell function, and cancer susceptibility. Diagnosis IBMFS presents major challenge due to the large variety associated phenotypes, novel, clinically relevant biomarkers urgently needed. Our study identified nuclear interaction partner ALK (NIPA) as an gene, it is significantly downregulated in distinct subset myelodysplastic syndrome-type (MDS-type)...
Anaplastic large-cell lymphoma (ALCL) is an aggressive non-Hodgkin that shows in 60% of cases a translocation t(2;5)(p23;q35), which leads to the expression oncogenic kinase NPM-ALK. The nuclear interaction partner ALK (NIPA) defines E3-SCF ligase contributes timing mitotic entry. It has been shown co-expression NIPA and NPM-ALK results constitutive phosphorylation. By mass spectrometry-based proteomics we identified nine serine/threonine residues be significantly upregulated upon...
Internal tandem duplications (ITD) of the FMS-like tyrosine kinase 3 (FLT3) predict poor prognosis in acute myeloid leukemia (AML) and often co-exist with inactivating DNMT3A mutations. In vitro studies implicated Grb2-associated binder 2 (GAB2) as FLT3-ITD effector. Utilizing a Flt3-ITD knock-in, Dnmt3a haploinsufficient mouse model, we demonstrate that Gab2 is essential for development driven AML vivo, deficient mice displayed prolonged survival, presented attenuated liver spleen pathology...
Abstract Introduction: BCL6 is a key oncogene in lymphoma pathogenesis. Malignant lymphoid cells exploit several mechanisms to deregulate the expression of BCL6, including chromosomal translocations, somatic mutations promoter regulatory regions, or inactivation pathway that controls its degradation. FBXO11 was recently identified as major ubiquitin ligase involved degradation and found be frequently inactivated by deletion diffuse large B cell (DLBCL). Thus, acts an oncosuppressor DLBCL...