A5068265508- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Hematological disorders and diagnostics
- Planarian Biology and Electrostimulation
- Mycobacterium research and diagnosis
- Acute Lymphoblastic Leukemia research
- Cancer Cells and Metastasis
- Mesenchymal stem cell research
- interferon and immune responses
- Multiple Myeloma Research and Treatments
- S100 Proteins and Annexins
- Sarcoma Diagnosis and Treatment
- Synthesis and Characterization of Heterocyclic Compounds
- Wireless Body Area Networks
- Pregnancy and preeclampsia studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA modifications and cancer
- Chronic Myeloid Leukemia Treatments
- Orthopedic Infections and Treatments
University of Padua
2019-2024
Woman's Hospital
2020
Mesenchymal stromal cells (MSCs) are key components of the tumor microenvironment (TME), influencing leukemia progression through poorly understood mechanisms. We investigated bioelectrical properties MSCs derived from pediatric AML patients (AML-MSCs) and identified a significant depolarization their resting membrane potential (Vmem, -14.7mV) compared to healthy (h-MSCs, -28.5mV), accompanied by downregulation CaV1.2 L-type calcium channel expression. AML-MSCs displayed increased...
In pediatric acute myeloid leukemia (AML), fusions involving lysine methyltransferase 2A (KMT2A) are considered hallmarks of aggressive AML, for whom the development targeted specific therapeutic agents to ameliorate classic chemotherapy and obtain a complete eradication disease is urgent. this study, we investigated antiapoptotic proteins in cohort 66 AML patients, finding that 75% KMT2A-r distributed Q3 + Q4 quartiles BCL-2 expression, have statistically significant high levels BCL-2,...
Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified long non-coding RNA CDK6-AS1 able cluster an AML subgroup peculiar gene signatures linked hematopoietic cell differentiation and mitochondrial dynamics. silencing triggered commitment in healthy CD34+ cells, whereas cells pathological undifferentiated state was rescued. This latter phenomenon derived...
In pediatric acute myeloid leukemia (AML), intensive chemotherapy and allogeneic hematopoietic stem cell transplantation are the cornerstones of treatment in high-risk cases, with severe late effects a still high risk disease recurrence as main drawbacks. The identification targeted, more effective, safer drugs is thus desirable. We performed high-throughput drug-screening assay 1280 compounds identified thioridazine (TDZ), drug that was highly selective for t(6;11)(q27;q23) MLL-AF6...
Hematopoietic stem cell transplantation (HSCT) is a curative post-remission treatment in patients with acute myeloid leukemia (AML), but relapse after transplant still challenging event. In recent year, several studies have investigated the molecular minimal residual disease (qPCR-MRD) as predictor of relapse, lack standardized protocols, cut-offs, and timepoints, especially pediatric setting, has prevented its use settings, including before HSCT. Here, we propose first collaborative...
Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, predominantly located in the nucleolus, that regulates multiplicity of different biological processes. NPM1 localization cell finely tuned by specific signal motifs, with two tryptophan residues (Trp) being essential for nucleolar localization. In acute myeloid leukemia (AML), several mutations have been reported, all resulting cytoplasmic delocalization, but putative and clinical significance variants are still debated. We...
Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity, cumulatively portend a more favorable outcome, but biology and prognostic implications different not extensively studied. In this multicentric study, we investigated the impact genotypes on patient's outcomes interrogated underlying subtypes. Of than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, COG trials),...
Background: In pediatric acute myeloid leukemia (AML), fusions involving lysine methyltransferase 2A (KMT2A) are considered hallmarks of aggressive AML, representing a challenge for the development targeted specific therapeutic agents to ameliorate classic chemotherapy and obtain complete eradication disease. Among them, t(9;11)KMT2A::MLLT3 represents most recurrent rearrangement, whereas t(6;11)KMT2A::AFDN-r is associated with dismal prognosis below 25%. We previously described KMT2A-AFDN...
Background: Pediatric acute myeloid leukemia (AML) is a life-threatening disease with chemotherapy and hematopoietic stem cell transplantation still representing the standard of care. Nowadays, most children affected from AML reached complete remission, but 30% experienced relapse indicating an urgent need to identify more effective therapies treat resistance recurrence events. In last years, genomic characterization improved success in identification molecularly targeted compounds....
Background: Diagnosis, treatment, minimal residual disease monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decade, although chemotherapy is still pillar treatment. Most emerged anti‐leukemic agents failed experimentation, one main limit in AML field inappropriateness current pre‐clinical models used to study drug efficacy, reducing advance phase II III clinical trials, especially for children. Aims: Set up characterization long...
Background: In pediatric acute myeloid leukemia (AML) chemotherapy is the standard of care, but >25% patients still relapse and after a disease recurrence survival probability extremely low (<50%). To ameliorate patients’ outcome there an urgent need to discover new treatments. Nevertheless, drug development reduced by better understanding adverse event profile adult cancer indications in children, lack pediatric-specific formulations, number AML that can be included clinical trials. Thus,...
Background: Relapse still represents an unsolved problem for children with acute myeloid leukemia (AML), therefore more effective therapeutic strategies are needed a complete blasts eradication. Leukemic stem cells (LSCs) have been proposed as the therapy-resistant reservoir of responsible failure antiproliferative chemotherapy and disease recurrence in AML due to their self-renewal capacity quiescence allowing evasion from chemotherapy. Thus, identification LSCs-specific vulnerabilities is...
Background: Bone marrow (BM) niche sustains hematopoiesis and hematopoietic stem cells (HSCs) homeostasis, but at Acute Myeloid Leukemia (AML) onset it undergoes to drastic remodeling support the disease, thus impeding HSCs functions. To date, underlying mechanisms interactions within BM are not clear, several line of evidences suggest that mesenchymal stromal (MSCs)-derived soluble factors play a key role in suppressing activity strongly contributing emergence an AML-infiltrated increasing...