0000000000025684

AUTHOR

Manlio Ferrarini

showing 9 related works from this author

Differentiation on Biological Basis of Monoclonal B-Cell Lymphocytosis (MBL) From Chronic Lymphocytic Leukemia (CLL): Results of a Prospective GISL (…

2010

Abstract Abstract 1360 The arbitrary cut-off of 5000/μL chronic lymphocytic leukemia (CLL)-phenotype cells in peripheral blood is generally used to separate monoclonal B-cell lymphocytosis (MBL) from CLL. However, a major concern is the biological differentiation, if any, between MBL and CLL. We tried to address the issue therefore analyzing 261 Rai stage 0 patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) prospective multicentre trial designed to validate biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk. In this cohort, biological charact…

Oncologymedicine.medical_specialtyLymphocytosisbusiness.industryChronic lymphocytic leukemiaImmunologyCell BiologyHematologymedicine.diseaseBiochemistryPeripheral bloodhemic and lymphatic diseasesInternal medicineMonoclonalCohortmedicineAlemtuzumabMonoclonal B-cell lymphocytosisStage (cooking)medicine.symptombusinessmedicine.drugBlood
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Microenvironment Regulation of IL23R/IL-23 Axis Drives Chronic Lymphocytic Leukemia (CLL) Progression

2015

Abstract Background : CLL displays a considerable degree of clinical heterogeneity, which is in part ascribable to clone-intrinsic biological features and that are also influenced by clone-extrinsic events related to the microenvironment. Among the dynamics-taking place within the CLL microenvironment, those finalized to the induction of an overly inflammatory milieu may significantly impact on the CLL natural history by hijacking the immunological microenvironment at the same time fostering clone fitness. IL-23 acts as a prototypical pro-inflammatory mediator representing a promising therapeutic target. We analyzed the ability of CLL cells to sense IL-23 through the IL-23R complex (consist…

CD40biologymedicine.diagnostic_testChronic lymphocytic leukemiaImmunologyClone (cell biology)CD28Cell BiologyHematologymedicine.diseaseBiochemistryCD19Flow cytometryLymphocyte costimulationbiology.proteinmedicineCancer researchCD5Blood
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miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone di…

2013

Skeletal homeostasis relies upon a fine tuning of osteoclast (OCLs)-mediated bone resorption and osteoblast (OBLs)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease. Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells,…

Bone diseasePhysiologyCellular differentiationCathepsin KClinical BiochemistryGene ExpressionOsteoclastsOsteolysisMMP9Cathepsin KCells CulturedTartrate-resistant acid phosphataseTumorCulturedReceptor Activator of Nuclear Factor-kappa BGenes fosCell DifferentiationOsteoblastCell biologyIsoenzymesmultiple myelomamedicine.anatomical_structureMatrix Metalloproteinase 9osteoclastMatrix Metalloproteinase 2medicine.medical_specialtyfosCellsAcid PhosphataseBiologyCollagen Type IBone resorptionCell LineOsteoclastCell Line TumorInternal medicinemedicineHumansBone ResorptionOsteoblastsmicroRNA.NFATC Transcription FactorsTartrate-Resistant Acid PhosphatasemiR-29bCell Biologymedicine.diseaseActinsMicroRNAsEndocrinologyGenesAcid Phosphatase; Actins; Bone Resorption; Cathepsin K; Cell Differentiation; Cell Line Tumor; Cells Cultured; Collagen Type I; Gene Expression; Genes fos; Humans; Isoenzymes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; MicroRNAs; Multiple Myeloma; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteolysis; Receptor Activator of Nuclear Factor-kappa BJournal of Cellular Physiology
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Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study

2021

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OncologyMalechronic B cell leukemiachronic lymphocytic leukemia; ibrutinib; 4-factor score; prognosis.Datasets as TopicSeverity of Illness Indexchemistry.chemical_compoundPiperidinesRetrospective analysisMulticenter Studies as TopicChronicLeukemiaHematologyMiddle AgedPrognosisLymphocyticProgression-Free SurvivalIbrutinibFemalemedicine.medical_specialtyreal-word studyFactor scoreAntineoplastic AgentsAdenine; Aged; Antineoplastic Agents; Datasets as Topic; Female; Follow-Up Studies; Humans; Leukemia Lymphocytic Chronic B-Cell; Male; Middle Aged; Multicenter Studies as Topic; Piperidines; Prognosis; Progression-Free Survival; Proportional Hazards Models; Protein Kinase Inhibitors; Reproducibility of Results; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival AnalysisRisk AssessmentNOibrutinibInternal medicineSeverity of illnessmedicineHumansProgression-free survivalProtein Kinase InhibitorsSurvival analysisAgedProportional Hazards ModelsRetrospective Studiesbusiness.industryProportional hazards modelAdenineB-CellReproducibility of ResultsRetrospective cohort studyAdenine; Aged; Antineoplastic Agents; Datasets as Topic; Female; Follow-Up Studies; Humans; Leukemia Lymphocytic Chronic B-Cell; Male; Middle Aged; Multicenter Studies as Topic; Piperidines; Prognosis; Progression-Free Survival; Proportional Hazards Models; Protein Kinase Inhibitors; Reproducibility of Results; Retrospective Studies; Risk Assessment; Survival Analysis; Severity of Illness IndexLeukemia Lymphocytic Chronic B-CellSurvival AnalysisSettore MED/15 - MALATTIE DEL SANGUEchemistrybusinesschronic lymphocytic leukaemiaFollow-Up Studies
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The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.

2011

AbstractIdentification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated …

MaleChronic lymphocytic leukemiaMICROENVIRONMENTPROGRESSIONCD38GUIDELINESBiochemistryCohort StudiesBone MarrowLYMPHOMAMedicineAged 80 and overHematologyMiddle AgedPrognosisLeukemiaB-CELLSMonoclonalDisease ProgressionBiological MarkersFemaleIGHV@AlgorithmsAdultmedicine.medical_specialtyDISORDERSB-CELLS; CLINICAL-SIGNIFICANCE; CD38 EXPRESSION; LYMPHOMA; CLL; MICROENVIRONMENT; PROGRESSION; GUIDELINES; DISORDERS; DIAGNOSISImmunologyImmunoglobulin light chainDIAGNOSISImmunoglobulin kappa-ChainsImmunoglobulin lambda-ChainsHumansCLINICAL-SIGNIFICANCESurvival analysisAgedbusiness.industryCytogeneticsCell Biologymedicine.diseaseLeukemia Lymphocytic Chronic B-CellSurvival AnalysisCD38 EXPRESSIONImmunologyCancer researchImmunoglobulin Light ChainsLymph NodesbusinessSettore MED/15 - Malattie del SangueBiomarkersCLLFollow-Up Studies
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The Pro-Inflammatory IL23/IL23R/IL17 Axis Is Active in IL23R-Expressing Circulating CLL Cells in Patients with Poor Prognosis

2012

Abstract Abstract 3889 Inflammatory cytokines play a biological role in the pathogenesis of Chronic lymphocytic leukemia (CLL). IL23 is a pro-inflammatory cytokine involved in T-cell responses and in tissue remodeling. It has been shown that the IL23 receptor (IL23R) is up-regulated in primary acute lymphoblastic leukemia (ALL) cells, and that IL23 inhibits ALL cell growth. Nevertheless, the anti-tumor function of IL23 still remains controversial. The role of the IL23R/IL23 axis in CLL has not been investigated so far. Herein we evaluated the expression pattern of IL23R/IL23 axis and its correlation with progression free survival (PFS) in CLL patients. A total of 233 newly diagnosed Binet s…

musculoskeletal diseasesPathologymedicine.medical_specialtyChronic lymphocytic leukemiaImmunologyContext (language use)Cell BiologyHematologyCD38Biologymedicine.diseaseBiochemistrymedicine.anatomical_structureAcute lymphocytic leukemiamedicineImmunohistochemistryBone marrowProgression-free survivalLymph nodeBlood
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MiR-146b-5p regulates IL-23 receptor complex expression in chronic lymphocytic leukemia cells

2022

Abstract Chronic lymphocytic leukemia (CLL) cells express the interleukin-23 receptor (IL-23R) chain, but the expression of the complementary IL-12Rβ1 chain requires cell stimulation via surface CD40 molecules (and not via the B-cell receptor [BCR]). This stimulation induces the expression of a heterodimeric functional IL-23R complex and the secretion of IL-23, initiating an autocrine loop that drives leukemic cell expansion. Based on the observation in 224 untreated Binet stage A patients that the cases with the lowest miR-146b-5p concentrations had the shortest time to first treatment (TTFT), we hypothesized that miR-146b-5p could negatively regulate IL-12Rβ1 side chain expression and clo…

MiceMicroRNAsCD40 LigandAnimalsReceptors Antigen B-CellChronic lymphocytic leukemia interleukin-23 receptor (IL-23R) MiR-146bSettore MED/05 - Patologia ClinicaRNA MessengerHematologySettore MED/08 - Anatomia PatologicaInterleukin-23Leukemia Lymphocytic Chronic B-CellBlood Advances
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Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features …

2014

Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and present at high concentrations in the sera of patients with chronic lymphocytic leukemia, prolongs the survival of leukemic B cells by interacting with their receptor, c-MET. It is, however, unknown whether hepatocyte growth factor influences microenvironmental cells, such as nurse-like cells, which deliver survival signals to the leukemic clone. We evaluated the expression of c-MET on nurse-like cells and monocytes from patients with chronic lymphocytic leukemia and searched for phenotypic/functional features supposed to be influenced by the hepatocyte growth factor/c-MET interaction. c-MET is expressed at hi…

STAT3 Transcription FactorC-MetStromal cellmedicine.medical_treatmentGene ExpressionBiologyMonocyteschemistry.chemical_compoundT-Lymphocyte SubsetsmedicineHumansIndoleamine-Pyrrole 23-DioxygenaseGrowth factor receptor inhibitorPhosphorylationIndoleamine 23-dioxygenaseCells CulturedFollicular dendritic cellsMacrophagesGrowth factorArticlesHematologyProto-Oncogene Proteins c-metLeukemia Lymphocytic Chronic B-CellCoculture TechniquesInterleukin-10C-MET; INDOLEAMINE 23-DIOXYGENASEchronic lymphocytic leukemia hepatocyte growth factor c-MET nurse-like cellshepatocyte growth factornurse-like cellschemistryHepatocyte Growth Factor ReceptorCancer researchchronic lymphocytic leukemiaHepatocyte growth factorC-METINDOLEAMINE 23-DIOXYGENASEmedicine.drugHaematologica
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Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

2018

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rβ1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rβ1 chain when cocultured with activated T cells or CD40L+ cells. CLL cells activated in…

0301 basic medicineStromal cellChronic lymphocytic leukemiaBiologyInterleukin-2303 medical and health sciencesParacrine signallingMice0302 clinical medicineRisk Factorshemic and lymphatic diseasesCell Line TumormedicineTumor MicroenvironmentAnimalsHumansAutocrine signallingCell ProliferationNeoplasm StagingTumor microenvironmentCD40Medicine (all)InterleukinGeneral MedicineReceptors Interleukinmedicine.diseaseAntibodies NeutralizingLeukemia Lymphocytic Chronic B-CellUp-RegulationLeukemia030104 developmental biology030220 oncology & carcinogenesisCancer researchbiology.proteinLymph NodesStromal CellsSignal Transduction
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