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Article ; Online: Differential diagnosis between kaposi sarcoma-associated herpesvirus cytokine syndrome and hemophagocytic lymphohistiocytosis.

Luppi, Mario / Cona, Andrea / Barozzi, Patrizia / Riva, Giovanni / Mularoni, Alessandra

2024

Language	English
Publishing date	2024-03-29
Publishing country	Germany
Document type	Letter
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-024-02252-7
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Zs.A 881: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Adverse outcome associated with daratumumab-based treatments in relapsed/refractory multiple myeloma patients with amplification of chromosome arm 1q21: a single-center retrospective experience.

Barbieri, Emiliano / Maccaferri, Monica / Leonardi, Giovanna / Giacobbi, Francesca / Corradini, Giorgia / Lagreca, Ivana / Barozzi, Patrizia / Potenza, Leonardo / Marasca, Roberto / Luppi, Mario

Annals of hematology

2022 Volume 101, Issue 12, Page(s) 2777–2779

MeSH term(s)	Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Chromosomes ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Neoplasms, Plasma Cell ; Retrospective Studies
Chemical Substances	daratumumab (4Z63YK6E0E)
Language	English
Publishing date	2022-09-15
Publishing country	Germany
Document type	Letter
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-022-04978-6
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Article ; Online: Improved efficacy of quizartinib in combination therapy with PI3K inhibition in primary FLT3-ITD AML cells.

Darici, Salihanur / Jørgensen, Heather G / Huang, Xu / Serafin, Valentina / Antolini, Ludovica / Barozzi, Patrizia / Luppi, Mario / Forghieri, Fabio / Marmiroli, Sandra / Zavatti, Manuela

Advances in biological regulation

2023 Volume 89, Page(s) 100974

Abstract: Acute myeloid leukemia is a heterogeneous hematopoietic malignancy, characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells, with poor outcomes. The internal tandem duplication (ITD) mutation of the Fms-like receptor ... ...

Abstract	Acute myeloid leukemia is a heterogeneous hematopoietic malignancy, characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells, with poor outcomes. The internal tandem duplication (ITD) mutation of the Fms-like receptor tyrosine kinase 3 (FLT3) (FLT3-ITD) represents the most common genetic alteration in AML, detected in approximately 30% of AML patients, and is associated with high leukemic burden and poor prognosis. Therefore, this kinase has been regarded as an attractive druggable target for the treatment of FLT3-ITD AML, and selective small molecule inhibitors, such as quizartinib, have been identified and trialled. However, clinical outcomes have been disappointing so far due to poor remission rates, also because of acquired resistance. A strategy to overcome resistance is to combine FLT3 inhibitors with other targeted therapies. In this study, we investigated the preclinical efficacy of the combination of quizartinib with the pan PI3K inhibitor BAY-806946 in FLT3-ITD cell lines and primary cells from AML patients. We show here that BAY-806946 enhanced quizartinib cytotoxicity and, most importantly, that this combination increases the ability of quizartinib to kill CD34
MeSH term(s)	Humans ; Phosphatidylinositol 3-Kinases/genetics ; Benzothiazoles/pharmacology ; Benzothiazoles/therapeutic use ; Mutation ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/therapeutic use ; fms-Like Tyrosine Kinase 3/genetics ; fms-Like Tyrosine Kinase 3/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	quizartinib (7LA4O6Q0D3) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Benzothiazoles ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; Protein Kinase Inhibitors ; FLT3 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2023.100974
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Article: Preclinical Validation of an Advanced Therapy Medicinal Product Based on Cytotoxic T Lymphocytes Specific for Mutated Nucleophosmin (NPM1

De Cicco, Marica / Lagreca, Ivana / Basso, Sabrina / Barozzi, Patrizia / Muscianisi, Stella / Bianco, Alba / Riva, Giovanni / Di Vincenzo, Sara / Pulvirenti, Chiara / Sapuppo, Davide / Siciliano, Mariangela / Rosti, Vittorio / Candoni, Anna / Zecca, Marco / Forghieri, Fabio / Luppi, Mario / Comoli, Patrizia

Cancers

2023 Volume 15, Issue 10

Abstract: Acute myeloid leukemia (AML) with nucleophosmin ( ...

Abstract	Acute myeloid leukemia (AML) with nucleophosmin (
Language	English
Publishing date	2023-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15102731
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Article ; Online: BTK Inhibition Impairs the Innate Response Against Fungal Infection in Patients With Chronic Lymphocytic Leukemia.

Fiorcari, Stefania / Maffei, Rossana / Vallerini, Daniela / Scarfò, Lydia / Barozzi, Patrizia / Maccaferri, Monica / Potenza, Leonardo / Ghia, Paolo / Luppi, Mario / Marasca, Roberto

Frontiers in immunology

2020 Volume 11, Page(s) 2158

Abstract: Infections represent a cause of morbidity and mortality in patients affected by chronic lymphocytic leukemia (CLL). Introduction of new drugs in CLL clinical practice has showed impressive efficacy, in particular those targeting BTK. Among the consistent ...

Abstract	Infections represent a cause of morbidity and mortality in patients affected by chronic lymphocytic leukemia (CLL). Introduction of new drugs in CLL clinical practice has showed impressive efficacy, in particular those targeting BTK. Among the consistent clinical data, an increasing number of reports describing the occurrence of unexpected opportunistic fungal infections has been reported during treatment with ibrutinib in the first 6 months of treatment. The reason underlying manifestations of invasive fungal infections in patients treated with ibrutinib is still under investigation. Our study aimed to understand the impact of BTK inhibition on immune response to fungal infection mediated by macrophages and CD14+ monocytic population obtained from CLL patients. Exposure to ibrutinib and acalabrutinib reduced signaling pathways activated by Keypoints: •BTK inhibition affects a productive immune response of CLL-associated macrophages (NLC) during
MeSH term(s)	Adenine/analogs & derivatives ; Adenine/pharmacology ; Adenine/therapeutic use ; Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Aspergillosis/immunology ; Aspergillus fumigatus/physiology ; Humans ; Immunity, Innate ; Immunomodulation ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Macrophages/immunology ; Macrophages/microbiology ; Phagocytosis ; Piperidines/pharmacology ; Piperidines/therapeutic use ; Signal Transduction ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Antineoplastic Agents ; Piperidines ; Tumor Necrosis Factor-alpha ; ibrutinib (1X70OSD4VX) ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2) ; BTK protein, human (EC 2.7.10.2) ; Adenine (JAC85A2161)
Language	English
Publishing date	2020-08-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.02158
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Article ; Online: BTK Inhibitors Impair Platelet-Mediated Antifungal Activity.

Cells

2022 Volume 11, Issue 6

Abstract: In recent years, the introduction of new drugs targeting Bruton's tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were ... ...

Abstract	In recent years, the introduction of new drugs targeting Bruton's tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to
MeSH term(s)	Agammaglobulinaemia Tyrosine Kinase/metabolism ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Aspergillosis/drug therapy ; Aspergillosis/metabolism ; Blood Platelets/metabolism ; Humans ; Invasive Fungal Infections/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Antifungal Agents ; Protein Kinase Inhibitors ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
Language	English
Publishing date	2022-03-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11061003
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Article ; Online: The dynamic functions of IRF4 in B cell malignancies.

Maffei, Rossana / Fiorcari, Stefania / Atene, Claudio Giacinto / Martinelli, Silvia / Mesini, Nicolò / Pilato, Flora / Lagreca, Ivana / Barozzi, Patrizia / Riva, Giovanni / Nasillo, Vincenzo / Paolini, Ambra / Forghieri, Fabio / Potenza, Leonardo / Trenti, Tommaso / Tagliafico, Enrico / Luppi, Mario / Marasca, Roberto

Clinical and experimental medicine

2022 Volume 23, Issue 4, Page(s) 1171–1180

Abstract: The trajectory of B cell development goes through subsequent steps governed by complex genetic programs, strictly regulated by multiple transcription factors. Interferon regulatory factor 4 (IRF4) regulates key points from pre-B cell development and ... ...

Abstract	The trajectory of B cell development goes through subsequent steps governed by complex genetic programs, strictly regulated by multiple transcription factors. Interferon regulatory factor 4 (IRF4) regulates key points from pre-B cell development and receptor editing to germinal center formation, class-switch recombination and plasma cell differentiation. The pleiotropic ability of IRF4 is mediated by its "kinetic control", allowing different IRF4 expression levels to activate distinct genetic programs due to modulation of IRF4 DNA-binding affinity. IRF4 is implicated in B cell malignancies, acting both as tumor suppressor and as tumor oncogene in different types of precursors and mature B cell neoplasia. Here, we summarize the complexity of IRF4 functions related to different DNA-binding affinity, multiple IRF4-specific target DNA motif, and interactions with transcriptional partners. Moreover, we describe the unique role of IRF4 in acute leukemias and B cell mature neoplasia, focusing on pathogenetic implications and possible therapeutic strategies in multiple myeloma and chronic lymphocytic leukemia.
MeSH term(s)	Humans ; Germinal Center ; Cell Differentiation ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Neoplasms ; DNA/metabolism
Chemical Substances	Interferon Regulatory Factors ; DNA (9007-49-2)
Language	English
Publishing date	2022-12-10
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-022-00968-0
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Zs.A 5481: Show issues

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Article ; Online: Acute Myeloid Leukemia in Patients Living with HIV Infection: Several Questions, Fewer Answers.

Forghieri, Fabio / Nasillo, Vincenzo / Bettelli, Francesca / Pioli, Valeria / Giusti, Davide / Gilioli, Andrea / Mussini, Cristina / Tagliafico, Enrico / Trenti, Tommaso / Cossarizza, Andrea / Maffei, Rossana / Barozzi, Patrizia / Potenza, Leonardo / Marasca, Roberto / Narni, Franco / Luppi, Mario

International journal of molecular sciences

2020 Volume 21, Issue 3

Abstract: Both human immunodeficiency virus (HIV) infection and acute myeloid leukemia (AML) may be considered relatively uncommon disorders in the general population, but the precise incidence of AML in people living with HIV infection (PLWH) is uncertain. ... ...

Abstract	Both human immunodeficiency virus (HIV) infection and acute myeloid leukemia (AML) may be considered relatively uncommon disorders in the general population, but the precise incidence of AML in people living with HIV infection (PLWH) is uncertain. However, life expectancy of newly infected HIV-positive patients receiving anti-retroviral therapy (ART) is gradually increasing, rivaling that of age-matched HIV-negative individuals, so that the occurrence of AML is also expected to progressively increase. Even if HIV is not reported to be directly mutagenic, several indirect leukemogenic mechanisms, mainly based on bone marrow microenvironment disruption, have been proposed. Despite a well-controlled HIV infection under ART should no longer be considered per se a contraindication to intensive chemotherapeutic approaches, including allogeneic hematopoietic stem cell transplantation, in selected fit patients with AML, survival outcomes are still generally unsatisfactory. We discussed several controversial issues about pathogenesis and clinical management of AML in PLWH, but few evidence-based answers may currently be provided, due to the limited number of cases reported in the literature, mainly as case reports or small retrospective case series. Prospective multicenter clinical trials are warranted to more precisely investigate epidemiology and cytogenetic/molecular features of AML in PLWH, but also to standardize and further improve its therapeutic management.
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; Comorbidity ; Drug Therapy ; HIV Infections/drug therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy ; Survival Analysis ; Treatment Outcome
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2020-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21031081
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Article: How to Improve Prognostication in Acute Myeloid Leukemia with

Biomedicines

2021 Volume 9, Issue 8

Abstract: Acute myeloid leukemia (AML) carrying inv(16)/t(16;16), resulting in fusion ... ...

Abstract	Acute myeloid leukemia (AML) carrying inv(16)/t(16;16), resulting in fusion transcript
Language	English
Publishing date	2021-08-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9080953
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Article: Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges.

Riva, Giovanni / Nasillo, Vincenzo / Ottomano, Anna Maria / Bergonzini, Giuliano / Paolini, Ambra / Forghieri, Fabio / Lusenti, Beatrice / Barozzi, Patrizia / Lagreca, Ivana / Fiorcari, Stefania / Martinelli, Silvia / Maffei, Rossana / Marasca, Roberto / Potenza, Leonardo / Comoli, Patrizia / Manfredini, Rossella / Tagliafico, Enrico / Trenti, Tommaso / Luppi, Mario

Cancers

2021 Volume 13, Issue 18

Abstract: Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk ... ...

Abstract	Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCR-based techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies-from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL) to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)-providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings.
Language	English
Publishing date	2021-09-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13184582
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