A5014370854- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Cancer Treatment and Pharmacology
- HIV/AIDS drug development and treatment
- Hematopoietic Stem Cell Transplantation
- Biochemical and Molecular Research
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Molecular Biology Techniques and Applications
- Telomeres, Telomerase, and Senescence
- Histone Deacetylase Inhibitors Research
- Chemotherapy-induced cardiotoxicity and mitigation
- interferon and immune responses
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune cells in cancer
- Sphingolipid Metabolism and Signaling
Istituto di Ematologia di Bologna
2021-2025
University of Bologna
2014-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2021-2024
Institute of Pharmacology
2019
University of Veterinary Medicine
2019
Istituto Oncologico Romagnolo
2015
Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis old or unfit remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested efficacy and safety of ponatinib plus prednisone in newly diagnosed Ph+ ALL ≥60 years, intensive chemotherapy stem cell transplantation. Forty-four received oral 45 mg/d 48 weeks (core phase), tapered to 60...
Despite the recent progress that has been made in understanding and treatment of acute lymphoblastic leukemia (ALL), outcome is still dismal adult ALL cases. Several studies solid tumors identified high expression WEE1 kinase as a poor prognostic factor reported its role cancer-conserving oncogene protects cancer cells from DNA damage. Therefore, targeted inhibition emerged rational strategy to sensitize antineoplastic compounds, which we evaluate this study. The effectiveness selective...
Monosomy 7 and deletion 7q are common chromosomal abnormalities in myeloid malignancies, they associated with a poor prognosis. The mechanism underlying their acquisition remains elusive. We identified cohort of 24 patients exhibiting clones different chromosome abnormalities, such as 7q, unstable derivatives (ring chromosomes or ‘naked’ centromeres), monosomy 7. designated this group having cytogenetic clonal evolution (CCE7). In some cases, CCE7 correlated disease progression, suggesting...
// Andrea Ghelli Luserna Di Rorà 1 , Ilaria Iacobucci 1, * Enrica Imbrogno Cristina Papayannidis Enrico Derenzini Anna Ferrari Viviana Guadagnuolo Valentina Robustelli Sarah Parisi Chiara Sartor Maria Abbenante Stefania Paolini Giovanni Martinelli Institute of Hematology "L. e A. Seragnoli", Department Experimental, Diagnostic and Specialty Medicine, University Bologna, Italy Co-corresponding authors Correspondence to: Iacobucci, email: ilaria.iacobucci2@unibo.it Martinelli,...
Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting progression and treatment response. The therapies available for AML can affect lymphocyte function, limiting efficacy immunotherapy while hindering leukemia-specific reactions. Recently, based on Venetoclax (VEN), a specific B-cell lymphoma 2 (BCL-2) inhibitor, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, has emerged as promising...
Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability and induces death in rapidly proliferating cells. Exploiting this finding a possible therapeutic approach showed efficacy various solid hematologic tumors, though not specifically tested acute lymphoblastic leukemia. Methods: The combination between inhibitors B T precursor leukemia (B/T-ALL) was evaluated vitro ex...
Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the
Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification these rare chimeras is interest to characterize patients. Here, we studied transcriptome 8 adult patients with poorly described chromosomal translocation(s), aim identifying novel transcripts. We integrated RNA-sequencing data multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization vitro...
Doxorubicin (Dox) is one of the most commonly used anthracyclines for treatment solid and hematological tumors such as B-/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication causes direct intercalating into double helix. Eukaryotic cells respond to by activating ATM-CHK2 and/or ATR-CHK1 pathway, whose function regulate cycle progression, promote damage repair, control apoptosis. We evaluated...
Extramedullary involvement of B-cell Acute Lymphoblastic Leukemia (EM-ALL) is a rare occurrence, characterized by dismal outcome and the absence defined shared therapeutic approach. In landscape innovative compounds, inotuzumab ozogamicin (IO) promising drug, whose mechanism action relies on killing CD22 positive leukemic cells, through delivery, after cell binding, molecule calicheamicin. We report two cases relapsed EM-ALL treated with IO, obtained as compassionate use. Case 1, 66 years...
Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related family. It secreted in vitro by endothelial cells vascular smooth muscle cells, significantly upregulated number of stimuli. Moreover, ADM participates regulation hematopoietic compartment, solid tumors leukemias, such as acute myeloid leukemia (AML). To better characterize involvement AML pathogenesis, we investigated its expression during human hematopoiesis leukemic subsets, based on...
Antigen-directed target therapy for B-cell acute lymphoblastic leukemia (B-ALL) is now the standard of care relapsed/refractory (R/R) disease. A comprehensive determination itself mandatory to aid physician's choice. We determined baseline Cluster differentiation 22 (CD22) expression percentage and fluorescent intensity on lymphoblasts 30 patients with R/R B-ALL treated anti-CD22 immunoconjugate drug Inotuzumab Ozogamicin (INO) analyzed impact both parameters patient outcome. Most (24/30,...
FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations FLT3 receptor include internal tandem duplications (ITD) that map to auto-inhibitory juxtamembrane (JM) domain or point within (TKD). Several inhibitors have been developed last few years, but midostaurin currently only one approved treatment newly diagnosed patients harboring mutations. Here we describe...
Somatic mutations of DNMT3A occur in about 20% acute myeloid leukemia (AML) patients. They mostly consist heterozygous missense targeting a hotspot site at R882 codon, which exhibit dominant negative effect and are associated with high myeloblast count, advanced age, poor prognosis. Other types such as truncations, insertions, or single-nucleotide deletion also affect the gene, though lower frequency. The present study aimed to characterize two gene identified by next-generation sequencing...
Abstract Doxorubicin (Dox) is one of the most commonly used anthracyclines for treatment solid and hematological tumors such as B-/T-cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase-II enzyme functionality, thus inducing structural damages during DNA replication causes direct intercalating into double helix. Eukaryotic cells respond to by activating ATM-CHK2 and/or ATR-CHK1 pathway, whose function regulate cell cycle progression, promote damage repair control apoptosis....
7038 Background: Nowadays, science is debating if autophagy in cancer can lead to therapy resistance or it favor apoptosis. Autophagy pathways are involved pro-apoptotic mechanism, they improve stresses survival eliminating damaged mitochondria and proteins. Levels activity of anti-apoptotic proteins (eg. bcl-2 p53), high levels cAMP, a pink/park complex could play as fulcrum on this lever. Our study aims define the role AML. Methods: We analyzed 148 consecutive non M3 AML with Affymetrix...