Maria Carmela Vegliante

Ospedale Oncologico "Giovanni Paolo II" di Bari | IRCCS Bari

Background: In Diffuse Large B-Cell Lymphoma (DLBCL), several methodologies are emerging to derive novel biomarkers to be incorporated in the risk assessment. We realized a pipeline that relies on autoencoders (AE) and Explainable Artificial Intelligence (XAI) to stratify prognosis and derive a gene-based signature. Methods: AE was exploited to lea...

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the d...

The role of macrophages (Mo) and their prognostic impact in diffuse large B‐cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver‐X‐receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein,...

The germinal center (GC) reaction results in the selection of B‐cells acquiring effector Ig secreting ability by progressing towards plasmablastic differentiation. This transition is associated with exclusion from the GC microenvironment. The aberrant expansion of plasmablastic elements within the GC fringes configures an atypical condition, the bi...

We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies.We included patients...

The unstructured nature of Real-World (RW) data from onco-hematological patients and the scarce accessibility to integrated systems restrain the use of RW information for research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports into standardized electronic health records. We exploited NLP to develop an aut...

Glutaminolysis is known to correlate with ovarian cancer aggressiveness and invasion. However, how this affects the tumor microenvironment is elusive. Here, we show that ovarian cancer cells become addicted to extracellular glutamine when silenced for glutamine synthetase (GS), similar to naturally occurring GS-low, glutaminolysis-high ovarian canc...

One of the main problems in the analysis of real data is often related to the presence of anomalies. Namely, anomalous cases can both spoil the resulting analysis and contain valuable information at the same time. In both cases, the ability to detect these occurrences is very important. In the biomedical field, a correct identification of outliers...

Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. Its classification encompasses a common form, also termed as “not otherwise specified” (NOS), and a series of variants, which are rare and at least in part related to viral agents. Over the last two decades, DLBCL-NOS, which...

The detection of gastrointestinal (GI) involvement in Mantle Cell Lymphoma is often underestimated and may have an impact on outcome and clinical management. We aimed to evaluate whether baseline 18F-FDG PET/CT presents comparable results to endoscopic biopsy in the diagnosis of GI localizations. In our retrospective cohort of 79 patients, sensitiv...

BACKGROUND The unstructured nature of medical data from Real-World (RW) patients and the scarce accessibility for researchers to integrated systems restrain the use of RW information for clinical and translational research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports in electronic health records (EHR),...

The oncogenic KRAS mutation has a critical role in the initiation of human pancreatic ductal adenocarcinoma (PDAC) since it rewires glutamine metabolism to increase reduced nicotinamide adenine dinucleotide phosphate (NADPH) production, balancing cellular redox homeostasis with macromolecular synthesis1,2. Mitochondrial glutamine-derived aspartate...

Background Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells...

Intra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenviro...

Among classical exemplifications of tumor microenvironment (TME) in lymphoma pathogenesis, the “effacement model” resembled by diffuse large B cell lymphoma (DLBCL) implies strong cell autonomous survival and paucity of non-malignant elements. Nonetheless, the magnitude of TME exploration is increasing as novel technologies allow the high-resolutio...

Background. Mantle-cell lymphoma (MCL) represents the 5-7% of all lymphoid malignancies. In 15-30% of cases by different data, MCL may affect the gastrointestinal tract (GI), but the real frequency by endoscopy and imaging could be significantly higher. Actually, by guidelines there are no recommendations for GI endoscopy in every patient with MCL....

Acetaminophen (APAP) is a worldwide commonly used painkiller drug. However, high doses of APAP can lead to acute hepatic failure and, in some cases, death. Previous studies indicated that different factors, including life-style and metabolic diseases, could predispose to the risk of APAP-induced liver failure. However, the molecular process that co...

The affiliations of authors T. Venesio and A. Sapino were originally incorrect. These have now been corrected as per the author listing above.

Background: Gene-expression-profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1,028-gene matrix incorpor...

Key Points SOX11 regulates MCL homing and invasion via direct regulation of CXCR4 and FAK expression and PI3K/AKT and ERK1/2 signaling activation. SOX11 expression increases CAM-DR, contributing to a more aggressive MCL phenotype.

Non-alcoholic fatty liver diseases are the hepatic manifestation of metabolic syndrome. According to the classical pattern of NAFLD progression, de novo fatty acid synthesis has been incriminated in NAFLD progression. However, this hypothesis has been challenged by the re-evaluation of NAFLD development mechanisms together with the description of t...

Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor superfamily. It is highly expressed in the enterohepatic system, where it senses bile acid levels to consequently reduce their synthesis while inducing their detoxification. Bile acids are intestinal tumor promoters and their concent...

SOX11 is overexpressed in several solid tumors and in the vast majority of aggressive mantle cell lymphomas (MCLs). We have recently proven that SOX11 silencing reduces tumor growth in a MCL xenograft model, consistent with the indolent clinical course of the human SOX11-negative mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms...

Mantle cell lymphoma (MCL) is an aggressive tumor but recent studies have identified a subtype of this lymphoma with an indolent clinical behavior and long survival of the patients even without chemotherapy that may correspond to a different clinical and biological subtype of the disease. These indolent MCLs differ from conventional MCLs in a parti...

Purpose: microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL). Experimental design: Expression...

Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms whose pathogenesis is not fully understood. The neural transcription factor SOX11 is overexpressed in most MCL but is not detected in other mature B-cell lymphomas or normal lymphoid cells. The specific expression of SOX11 in MCL suggests that it may be an important element...

Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course, whereas others having an indolent behavior. We conducted an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B-cell receptors (BcR) may identify different subsets of...

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with a median survival of the patients of 3–5 years.¹ This aggressive behavior has been related to its genetic and molecular pathogenesis that integrates the deregulation of cell proliferation due to the t(11;14)(q13;q32) and cyclin D1 overexpression, and the accumulation of a high number...

Analysis by bisulfite-pyrosequencing of the SOX11 promoter de-methylation in RAJI cells after being treated for 72 h with 1 µM AZA alone, in combination with 10 µM SAHA 24 h concluding the treatment with AZA or treated for 24 h with 10 µM of SAHA alone. (TIF)

SOX11 TEL-AML1 transduced cells. (XLS)

Cases and analyses. (XLS)

The specificity of the polyclonal antibody against SOX11 (1159) was verified by western blotting analysis. HEK293T cells were transfected with vectors encoding HA-SOX4, HA-SOX11 and with the empty vector pcDNA3.1 (CT). Twenty-four hours after transfection, cells were collected and protein extracts were subjected to immunoblotting with antibodies ag...

Supplemental Experimental Procedures. (DOC)

Scatter plot showing a correlation between DNA methylation percentages of the CpG site 1 quantified by bisulfite pyrosequencing and the values of the CpG analyzed by the Infinium array (cg20008332) (Rho Spearman coefficient = 0.902, p<0.001). (TIF)

Cases studied by Affymetrix gene expression arrays. (XLS)

SOX11 mouse-immunological genome project data. (XLS)

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 express...