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Article: The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer.

Cusenza, Vincenza Ylenia / Tameni, Annalisa / Neri, Antonino / Frazzi, Raffaele

2023 Volume 13, Page(s) 1063636

Abstract: Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1- ... ...

Abstract	Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2'-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as "writers", "readers" and "erasers". m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1063636
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Article: Incidence and Survival of Testicular Cancers in a Province in Northern Italy and Their Association with Second Tumors.

Mangone, Lucia / Marinelli, Francesco / Bisceglia, Isabella / Masini, Cristina / Palicelli, Andrea / Morabito, Fortunato / Di Girolamo, Stefania / Neri, Antonino / Pinto, Carmine

Biology

2023 Volume 12, Issue 11

Abstract: This study investigated the incidence, mortality, and 5-year survival rates of testicular cancers diagnosed in a northern Italian province, which were eventually associated with previous or subsequent extratesticular neoplasms. Cases from 1996 to 2020 ... ...

Abstract	This study investigated the incidence, mortality, and 5-year survival rates of testicular cancers diagnosed in a northern Italian province, which were eventually associated with previous or subsequent extratesticular neoplasms. Cases from 1996 to 2020 were examined by age and histotype (seminoma vs. non-seminoma). The standardized incidence rate was calculated using the European population, and the annual percent change (APC) was reported. The five-year relative survival was estimated using the Pohar Perme method. The association with the second neoplasm was also evaluated. In our study, 385 patients with testicular cancer were included, most of whom were aged between 30 and 40 years. The non-seminoma and seminoma groups accounted for 44% and 18% of younger adults, respectively. The incidence rate increased during the study period (APC 1.6); however, it increased in seminomas (APC 2.3) but not in non-seminomas (APC -0.1). Conversely, the mortality rate remained constantly low either overall or in each of the two groups. The overall 5-year survival rate of testicular cancer patients was 95% (99% and 88% for seminomas and non-seminomas, respectively). Primary extratesticular tumors were documented in 37 cases, 18 after and 19 before the testicular cancer diagnosis. Our study confirms that the increased incidence and excellent survival rate are the prerogative of seminomas.
Language	English
Publishing date	2023-11-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12111409
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Article ; Online: Venetoclax in acute myeloid leukemia.

Bruzzese, Antonella / Martino, Enrica Antonia / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Neri, Antonino / Morabito, Fortunato / Vigna, Ernesto / Gentile, Massimo

Expert opinion on investigational drugs

2023 Volume 32, Issue 4, Page(s) 271–276

MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/drug therapy ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols
Chemical Substances	venetoclax (N54AIC43PW) ; Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides
Language	English
Publishing date	2023-03-23
Publishing country	England
Document type	Editorial
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2023.2193679
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Article ; Online: Utilizing next-generation sequencing in the management of multiple myeloma.

Lionetti, Marta / Neri, Antonino

Expert review of molecular diagnostics

2017 Volume 17, Issue 7, Page(s) 653–663

Abstract: Introduction: Multiple myeloma (MM) is a bone marrow plasma cell malignancy characterized by wide clinical presentation and heterogeneous genetic background. Despite the recent advances in patient outcome, new markers are needed for improving risk ... ...

Abstract	Introduction: Multiple myeloma (MM) is a bone marrow plasma cell malignancy characterized by wide clinical presentation and heterogeneous genetic background. Despite the recent advances in patient outcome, new markers are needed for improving risk prediction and choice of a more appropriate therapy. In this perspective, the genetic makeup of MM cells is being better characterized by means of next-generation sequencing (NGS) technologies. Areas covered: The authors discuss how the application of NGS has improved our knowledge of MM biology by discovering its mutational landscape, identifying the operating mutational processes, and revealing the clonal composition of tumors and the dynamics of its evolution; and how this can have important clinical implications in terms of prognostication, therapeutic choices, and response assessment. Finally, the authors provide a quick outlook of future applications of these technologies that could help in the management of the disease in the next years. Expert commentary: The clinical exploitation of NGS-based characterization of MM patients has as its ultimate goal the precision medicine. Considerable obstacles to its implementation in myeloma management exist; therefore, the concerted effort of all involved stakeholders is mandatory to ensure that it will become a reality in routine clinical practice in the next future.
Language	English
Publishing date	2017-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1080/14737159.2017.1332996
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Article ; Online: Ivosidenib in acute myeloid leukemia.

Bruzzese, Antonella / Labanca, Caterina / Martino, Enrica Antonia / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Neri, Antonino / Imovilli, Annalisa / Morabito, Fortunato / Vigna, Ernesto / Gentile, Massimo

Expert opinion on pharmacotherapy

2024 Volume 24, Issue 18, Page(s) 2093–2100

Abstract: Introduction: Traditional treatment strategies for acute myeloid leukemia (AML) have primarily relied on standard chemotherapy regimens for four decades. Indeed, the landscape of AML therapy has evolved substantially in recent years, mainly due to the ... ...

Abstract	Introduction: Traditional treatment strategies for acute myeloid leukemia (AML) have primarily relied on standard chemotherapy regimens for four decades. Indeed, the landscape of AML therapy has evolved substantially in recent years, mainly due to the introduction of hypomethylating agents and small molecules.Bcl2 inhibitor venetoclax, Fms-like tyrosine kinase 3 (FLT3) inhibitors such as midostaurin and gilteritinib, and isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) inhibitors ivosidenib and enasidenib, as well as hedgehog (HH) pathway inhibitor glasdegib represented a significant step forward in AML therapeutic armamentarium. Smoothened (SMO) inhibitor in combination with low-dose cytarabine marks a recent milestone. Areas covered: Ivosidenib, the first-in-class, selective, allosteric IDH1R132 inhibitor, showed the capability to induce Expert opinion: The identified ivosidenib's strengths, including its remarkable safety record and ability to yield positive therapeutic outcomes, position it as an ideal partner for both classic chemotherapy and biological treatments, i.e. hypometilant agents and/or venetoclax. Further studies are warranted to explore strategies for overcoming the occurrence of ivosidenib resistance.
MeSH term(s)	Humans ; Hedgehog Proteins ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Pyridines/adverse effects ; Antineoplastic Agents/adverse effects ; Mutation
Chemical Substances	ivosidenib (Q2PCN8MAM6) ; venetoclax (N54AIC43PW) ; Hedgehog Proteins ; Pyridines ; Antineoplastic Agents
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2023.2272659
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Article ; Online: Potential of BGB-11417, a BCL2 inhibitor, in hematological malignancies.

Bruzzese, Antonella / Martino, Enrica Antonia / Labanca, Caterina / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Neri, Antonino / Morabito, Fortunato / Vigna, Ernesto / Gentile, Massimo

Expert opinion on investigational drugs

2024 Volume 33, Issue 2, Page(s) 73–77

MeSH term(s)	Humans ; Hematologic Neoplasms/drug therapy ; Hematologic Neoplasms/pathology ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Proto-Oncogene Proteins c-bcl-2
Chemical Substances	Antineoplastic Agents ; Proto-Oncogene Proteins c-bcl-2 ; BCL2 protein, human
Language	English
Publishing date	2024-01-26
Publishing country	England
Document type	Editorial
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2024.2309873
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Article ; Online: Momelotinib in myelofibrosis.

Bruzzese, Antonella / Martino, Enrica Antonia / Labanca, Caterina / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Zimbo, Annamaria / Fragliasso, Valentina / Neri, Antonino / Morabito, Fortunato / Vigna, Ernesto / Gentile, Massimo

Expert opinion on pharmacotherapy

2024 , Page(s) 1–8

Abstract: Introduction: Myelofibrosis (MF) is a hematologic disease characterized by bone marrow fibrosis, cytopenias, splenomegaly, and constitutional symptoms. Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, ...

Abstract	Introduction: Myelofibrosis (MF) is a hematologic disease characterized by bone marrow fibrosis, cytopenias, splenomegaly, and constitutional symptoms. Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, which target the Janus kinases (JAK) pathway. However, their myelosuppressive effect coupled with the persistence, and even worsening anemia remains a significant challenge, leading usually to treatment discontinuation. Areas covered: This review focuses on Momelotinib (MMB), a unique JAK inhibitor that has shown promise in MF treatment, particularly in improving anemia. MMB inhibits type 1 kinase activin A receptor or activin receptor-like kinase-2 (ACVR1/ALK2), with consequent rebalancing of the SMAD pathways and reduced transcription of hepcidin. Moreover, it seems that MMB could reduce the serum levels of several inflammatory cytokines responsible for anemia. Clinical trials have demonstrated MMB's efficacy in reducing spleen size, alleviating symptoms, and improving anemia, with a favorable safety profile compared to other JAK inhibitors, both in treatment-naïve and in pre-treated patients. Expert opinion: Due to its mechanism of action, MMB represents a valuable therapeutic option in MF, addressing the clinical challenge of anemia and potentially improving outcomes for patients with hematologic malignancies. Ongoing research explores MMB's potential in acute myeloid leukemia and combination therapies.
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2024.2343780
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Article ; Online: Whole-exome sequencing is feasible on a fresh-frozen skin sample of intravascular large B cell lymphoma.

Bagnoli, Filippo / Pini, Giuditta / Ziccheddu, Bachisio / Bonometti, Arturo / Alberti-Violetti, Silvia / Venegoni, Luigia / Isimbaldi, Giuseppe / Da Vià, Matteo Claudio / Ferrari, Angela / Baldini, Luca / Neri, Antonino / Onida, Francesco / Bolli, Niccolò / Berti, Emilio

Clinical and experimental medicine

2024 Volume 24, Issue 1, Page(s) 51

Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is ...

Abstract	Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions.
MeSH term(s)	Humans ; Exome Sequencing ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Non-Hodgkin ; Subcutaneous Tissue ; DNA
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2024-03-05
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-024-01308-0
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Article ; Online: Selinexor in multiple myeloma.

Martino, Enrica Antonia / Vigna, Ernesto / Bruzzese, Antonella / Labanca, Caterina / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Zimbo, Annamaria / Torricelli, Federica / Neri, Antonino / Morabito, Fortunato / Gentile, Massimo

Expert opinion on pharmacotherapy

2024 Volume 25, Issue 4, Page(s) 421–434

Abstract: Introduction: Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM).: Areas covered: This article provides a review of selinexor, with a focus on ... ...

Abstract	Introduction: Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM). Areas covered: This article provides a review of selinexor, with a focus on available clinical studies involving MM patients and its safety profile. Clinical trials, such as STORM and BOSTON, have demonstrated its efficacy, particularly in combination regimens, showcasing notable overall response rates (ORR) and prolonged median progressionfree survival (mPFS). Selinexor's versatility is evident across various combinations, including carfilzomibdexamethasone (XKd), lenalidomidedexamethasone (XRd), and pomalidomidedexamethasone (XPd), with efficacy observed even in tripleclass refractory and highrisk patient populations. However, challenges, including resistance mechanisms and adverse events, necessitate careful management. Realworld evidence also underscores selinexor's effectiveness in RRMM, though dose adjustments and supportive measures remain crucial. Ongoing trials are exploring selinexor in diverse combinations and settings, including pomalidomidenaïve patients and postautologous stem cell transplant (ASCT) maintenance. Expert opinion: The evolving landscape of selinexor's role in the sequencing of treatment for RRMM, its potential in highrisk patients, including those with extramedullary disease, as revealed in the most recent international meetings, and ongoing investigations signal a dynamic era in myeloma therapeutics. Selinexor emerges as a pivotal component in multidrug strategies and innovative combinations.
MeSH term(s)	Multiple Myeloma/drug therapy ; Humans ; Hydrazines/therapeutic use ; Hydrazines/adverse effects ; Triazoles/therapeutic use ; Triazoles/adverse effects ; Karyopherins/antagonists & inhibitors ; Exportin 1 Protein ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Progression-Free Survival
Chemical Substances	selinexor (31TZ62FO8F) ; Hydrazines ; Triazoles ; Karyopherins ; Exportin 1 Protein ; Receptors, Cytoplasmic and Nuclear ; Antineoplastic Agents
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2024.2333376
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Article ; Online: Myelodysplastic syndromes del(5q): Pathogenesis and its therapeutic implications.

Bruzzese, Antonella / Martino, Enrica Antonia / Mendicino, Francesco / Lucia, Eugenio / Olivito, Virginia / Capodanno, Isabella / Neri, Antonino / Morabito, Fortunato / Vigna, Ernesto / Gentile, Massimo

European journal of haematology

2024 Volume 112, Issue 6, Page(s) 860–869

Abstract: Myelodysplastic syndromes (MDS) encompass a heterogeneous set of acquired bone marrow neoplastic disorders characterized by ineffective hematopoiesis within one or more bone marrow lineages. Nearly half of MDS patients carry cytogenetic alterations, with ...

Abstract	Myelodysplastic syndromes (MDS) encompass a heterogeneous set of acquired bone marrow neoplastic disorders characterized by ineffective hematopoiesis within one or more bone marrow lineages. Nearly half of MDS patients carry cytogenetic alterations, with del(5q) being the most prevalent. Since its first description, del(5q) was consistently correlated with a typical clinical phenotype marked by anemia, thrombocytosis, and a low risk of evolving into acute leukemia. Presently, the World Health Organization (WHO) classification of myeloid neoplasms recognizes a specific subtype of MDS known as "myelodysplastic neoplasm with low blast and isolated del(5q)" identified by the sole presence of 5q deletion or in combination with one other abnormality excluding -7/del(7q). Several studies have sought to unravel the biological processes triggered by del(5q) in the development of MDS, revealing the involvement of various genes localized in specific regions of chromosome 5 referred to as common deleted regions (CDR). This intricate biological landscape makes the MDS cells with del(5q) exceptionally sensitive to lenalidomide. Several studies have confirmed the efficacy of lenalidomide in this context. Regrettably, the response to lenalidomide is not conclusive, prompting ongoing research into biological mechanisms that drive patients toward leukemia and strategies to circumvent lenalidomide resistance and disease progression.
MeSH term(s)	Humans ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/therapy ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/etiology ; Chromosome Deletion ; Chromosomes, Human, Pair 5/genetics ; Lenalidomide/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/pharmacology
Chemical Substances	Lenalidomide (F0P408N6V4) ; Antineoplastic Agents
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.14181
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