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Article ; Online: Characterization of a novel IDH2-R159H mutation in acute myeloid leukaemia: Effects on cell metabolism and differentiation.

Nardozza, Anna Maria / Guarnera, Luca / Travaglini, Serena / Ottone, Tiziana / Divona, Mariadomenica / De Bellis, Eleonora / Savi, Arianna / Banella, Cristina / Noguera, Nelida Ines / Di Fusco, Davide / Monteleone, Ivan / Voso, Maria Teresa

British journal of haematology

2023 Volume 204, Issue 2, Page(s) 719–723

MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/genetics ; Cell Differentiation ; Mutation ; Isocitrate Dehydrogenase/genetics
Chemical Substances	Isocitrate Dehydrogenase (EC 1.1.1.41)
Language	English
Publishing date	2023-11-27
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19216
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Article: Virus-to-prokaryote ratio in the Salar de Huasco and different ecosystems of the Southern hemisphere and its relationship with physicochemical and biological parameters.

Eissler, Yoanna / Castillo-Reyes, Alonso / Dorador, Cristina / Cornejo-D'Ottone, Marcela / Celis-Plá, Paula S M / Aguilar, Polette / Molina, Verónica

Frontiers in microbiology

2022 Volume 13, Page(s) 938066

Abstract: The virus-to-prokaryote ratio (VPR) has been used in many ecosystems to study the relationship between viruses and their hosts. While high VPR values indicate a high rate of prokaryotes' cell lysis, low values are interpreted as a decrease in or absence ... ...

Abstract	The virus-to-prokaryote ratio (VPR) has been used in many ecosystems to study the relationship between viruses and their hosts. While high VPR values indicate a high rate of prokaryotes' cell lysis, low values are interpreted as a decrease in or absence of viral activity. Salar de Huasco is a high-altitude wetland characterized by a rich microbial diversity associated with aquatic sites like springs, ponds, streams and a lagoon with variable physicochemical conditions. Samples from two ponds, Poza Rosada (PR) and Poza Verde (PV), were analyzed by epifluorescence microscopy to determine variability of viral and prokaryotic abundance and to calculate the VPR in a dry season. In addition, to put Salar de Huasco results into perspective, a compilation of research articles on viral and prokaryotic abundance, VPR, and metadata from various Southern hemisphere ecosystems was revised. The ecosystems were grouped into six categories: high-altitude wetlands, Pacific, Atlantic, Indian, and Southern Oceans and Antarctic lakes. Salar de Huasco ponds recorded similar VPR values (an average of 7.4 and 1.7 at PR and PV, respectively), ranging from 3.22 to 15.99 in PR. The VPR variability was associated with VA and chlorophyll
Language	English
Publishing date	2022-08-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.938066
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Article ; Online: Multifaceted control of adult SVZ neurogenesis by the vascular niche.

Ottone, Cristina / Parrinello, Simona

Cell cycle (Georgetown, Tex.)

2015 Volume 14, Issue 14, Page(s) 2222–2225

Abstract: The subventricular zone is one of the 2 germinal niches of the adult brain where neural stem cells (NSC) generate new neurons and glia throughout life. NSC behavior is controlled by the integration of intrinsic signals and extrinsic cues provided by the ... ...

Abstract	The subventricular zone is one of the 2 germinal niches of the adult brain where neural stem cells (NSC) generate new neurons and glia throughout life. NSC behavior is controlled by the integration of intrinsic signals and extrinsic cues provided by the surrounding microenvironment, or niche. Within the niche, the vasculature has emerged as a critical compartment, to which both neural stem cells and transit-amplifying progenitors are closely associated. A key function of the vasculature is to deliver blood-borne and secreted factors that promote proliferation and lineage progression of committed neural progenitors. We recently found that, in contrast to the established role of soluble cues, juxtacrine signals on vascular endothelial cells maintain neural stem cells in a quiescent and undifferentiated state through direct cell-cell interactions. In this perspective, we discuss how, through these apparently opposing signals, the vascular niche might coordinate stem cell decisions between maintenance and proliferation.
MeSH term(s)	Brain-Derived Neurotrophic Factor/metabolism ; Calcium-Binding Proteins/metabolism ; Chemokine CXCL12/metabolism ; Ephrin-B2/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins/metabolism ; Nerve Growth Factors/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis ; Neurons/cytology ; Neurons/metabolism ; Neurotrophin 3 ; Paracrine Communication ; Serrate-Jagged Proteins ; Stem Cell Niche
Chemical Substances	Brain-Derived Neurotrophic Factor ; CXCL12 protein, human ; Calcium-Binding Proteins ; Chemokine CXCL12 ; Ephrin-B2 ; Intercellular Signaling Peptides and Proteins ; Membrane Proteins ; NTF3 protein, human ; Nerve Growth Factors ; Neurotrophin 3 ; Serrate-Jagged Proteins ; BDNF protein, human (7171WSG8A2)
Language	English
Publishing date	2015-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2015.1049785
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Article ; Online: Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer.

Davies, Gareth C G / Dedi, Neesha / Jones, Paul S / Kevorkian, Lara / McMillan, David / Ottone, Cristina / Schulze, Monika-Sarah E D / Scott-Tucker, Anthony / Tewari, Roohi / West, Shauna / Wright, Michael / Rowley, Tania F

mAbs

2023 Volume 15, Issue 1, Page(s) 2289681

Abstract: Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range ...

Abstract	Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range of cancer types. A lack of published work using therapeutic modalities has precluded the testing of the hypothesis that blocking the gremlin-1/BMP interaction will provide benefits to patients. To address this shortfall, we developed ginisortamab (UCB6114), a first-in-class clinical anti-human gremlin-1 antibody, currently in clinical development for the treatment of cancer, along with its murine analog antibody Ab7326 mouse immunoglobulin G1 (mIgG1). Surface plasmon resonance assays revealed that ginisortamab and Ab7326 mIgG1 had similar affinities for human and mouse gremlin-1, with mean equilibrium dissociation constants of 87 pM and 61 pM, respectively. The gremlin-1/Ab7326 antigen-binding fragment (Fab) crystal structure revealed a gremlin-1 dimer with a Fab molecule bound to each monomer that blocked BMP binding. In cell culture experiments, ginisortamab fully blocked the activity of recombinant human gremlin-1, and restored BMP signaling pathways in human colorectal cancer (CRC) cell lines. Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298).
MeSH term(s)	Humans ; Animals ; Mice ; Cell Line ; Signal Transduction ; Neoplasms/drug therapy ; Tumor Microenvironment
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2537838-7
ISSN	1942-0870 ; 1942-0870
ISSN (online)	1942-0870
ISSN	1942-0870
DOI	10.1080/19420862.2023.2289681
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Article ; Online: Recovery of humic acids from anaerobic sewage sludge: Extraction, characterization and encapsulation in alginate beads.

Cristina, Giulio / Camelin, Enrico / Ottone, Carminna / Fraterrigo Garofalo, Silvia / Jorquera, Lorena / Castro, Mónica / Fino, Debora / Schiappacasse, María Cristina / Tommasi, Tonia

International journal of biological macromolecules

2020 Volume 164, Page(s) 277–285

Abstract: Wastewater production is rising all over the world and one of the most difficult problems is the disposal of sewage sludge (SS). It is known that SS contains certain quantities of added-value compounds, such as humic acids (HA) which in turn have ... ...

Abstract	Wastewater production is rising all over the world and one of the most difficult problems is the disposal of sewage sludge (SS). It is known that SS contains certain quantities of added-value compounds, such as humic acids (HA) which in turn have beneficial effects on soil quality and plant growth. On the other hand, SS can retain many pollutants, such as heavy metals. The present work aimed to implement an HA alkaline extraction protocol from anaerobic sewage sludge (ASS). Subsequently, the HA were quantified in ASS, in HA extract and in commercial HA, used as a benchmark, which gave results of 12.53%, 26.87% and 77.87% (on dry matter basis), respectively. FESEM and EDX analyses on lyophilized HA extract confirmed that no heavy metals had passed into the extract. Afterwards, in order to allow controlled release of the HA in soils, alginate beads containing the HA extract were created. Finally, a pot experiment in a greenhouse was performed using Chilean lettuce plants (Lactuca sativa L.) treated with alginate-HA extract beads. At the end of the greenhouse experiments, the hypogean dry biomass of the treated plants was significantly higher than for non-treated plants. The relevance of this study relies not only on the exploitation of green chemistry principles, by converting a waste stream into a high-value product, but also on the application of an approach following a circular economy model.
MeSH term(s)	Alginates/chemistry ; Anaerobiosis ; Chemical Fractionation ; Chemical Phenomena ; Humic Substances ; Microspheres ; Sewage/chemistry ; Spectroscopy, Fourier Transform Infrared
Chemical Substances	Alginates ; Humic Substances ; Sewage
Language	English
Publishing date	2020-07-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.07.097
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Article ; Online: MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs' patients.

Catalano, Gianfranco / Zaza, Alessandra / Banella, Cristina / Pelosi, Elvira / Castelli, Germana / de Marinis, Elisabetta / Smigliani, Ariela / Travaglini, Serena / Ottone, Tiziana / Divona, Mariadomenica / Del Principe, Maria Ilaria / Buccisano, Francesco / Maurillo, Luca / Ammatuna, Emanuele / Testa, Ugo / Nervi, Clara / Venditti, Adriano / Voso, Maria Teresa / Noguera, Nelida Ines

Leukemia

2023 Volume 37, Issue 8, Page(s) 1600–1610

Abstract: We characterize the metabolic background in distinct Acute Myeloid Leukemias (AMLs), by comparing the metabolism of primary AML blasts isolated at diagnosis with that of normal hematopoietic maturing progenitors, using the Seahorse XF Agilent. Leukemic ... ...

Abstract	We characterize the metabolic background in distinct Acute Myeloid Leukemias (AMLs), by comparing the metabolism of primary AML blasts isolated at diagnosis with that of normal hematopoietic maturing progenitors, using the Seahorse XF Agilent. Leukemic cells feature lower spare respiratory (SRC) and glycolytic capacities as compared to hematopoietic precursors (i.e. day 7, promyelocytes). According with Proton Leak (PL) values, AML blasts can be grouped in two well defined populations. The AML group with blasts presenting high PL or high basal OXPHOS plus high SRC levels had shorter overall survival time and significantly overexpressed myeloid cell leukemia 1 (MCL1) protein. We demonstrate that MCL1 directly binds to Hexokinase 2 (HK2) on the outer mitochondrial membrane (OMM). Overall, these results suggest that high PL and high SRC plus high basal OXPHOS levels at disease onset, arguably with the concourse of MCL1/HK2 action, are significantly linked with shorter overall survival time in AML. Our data describe a new function for MCL1 protein in AMLs' cells: by forming a complex with HK2, MCL1 co-localizes to VDAC on the OMM, thus inducing glycolysis and OXPHOS, ultimately conferring metabolic plasticity and promoting resistance to therapy.
MeSH term(s)	Humans ; Hexokinase ; Leukemia, Myeloid, Acute ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism
Chemical Substances	Hexokinase (EC 2.7.1.1) ; MCL1 protein, human ; Myeloid Cell Leukemia Sequence 1 Protein ; HK2 protein, human (EC 2.7.1.1)
Language	English
Publishing date	2023-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-01946-5
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Article: Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis.

Guarnera, Luca / Ottone, Tiziana / Fabiani, Emiliano / Divona, Mariadomenica / Savi, Arianna / Travaglini, Serena / Falconi, Giulia / Panetta, Paola / Rapanotti, Maria Cristina / Voso, Maria Teresa

Frontiers in oncology

2022 Volume 12, Page(s) 871590

Abstract: Acute promyelocytic leukemia (APL) accounts for 10-15% of newly diagnosed acute myeloid leukemias (AML) and is typically caused by the fusion of promyelocytic leukemia with retinoic acid receptor α ( ...

Abstract	Acute promyelocytic leukemia (APL) accounts for 10-15% of newly diagnosed acute myeloid leukemias (AML) and is typically caused by the fusion of promyelocytic leukemia with retinoic acid receptor α (
Language	English
Publishing date	2022-04-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.871590
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Article: Recovery of humic acids from anaerobic sewage sludge: Extraction, characterization and encapsulation in alginate beads

Cristina, Giulio / Camelin, Enrico / Ottone, Carminna / Fraterrigo Garofalo, Silvia / Jorquera, Lorena / Castro, Mónica / Fino, Debora / Schiappacasse, María Cristina / Tommasi, Tonia

International journal of biological macromolecules. 2020 Dec. 01, v. 164

2020

Abstract	Wastewater production is rising all over the world and one of the most difficult problems is the disposal of sewage sludge (SS). It is known that SS contains certain quantities of added-value compounds, such as humic acids (HA) which in turn have beneficial effects on soil quality and plant growth. On the other hand, SS can retain many pollutants, such as heavy metals. The present work aimed to implement an HA alkaline extraction protocol from anaerobic sewage sludge (ASS). Subsequently, the HA were quantified in ASS, in HA extract and in commercial HA, used as a benchmark, which gave results of 12.53%, 26.87% and 77.87% (on dry matter basis), respectively. FESEM and EDX analyses on lyophilized HA extract confirmed that no heavy metals had passed into the extract. Afterwards, in order to allow controlled release of the HA in soils, alginate beads containing the HA extract were created. Finally, a pot experiment in a greenhouse was performed using Chilean lettuce plants (Lactuca sativa L.) treated with alginate-HA extract beads. At the end of the greenhouse experiments, the hypogean dry biomass of the treated plants was significantly higher than for non-treated plants. The relevance of this study relies not only on the exploitation of green chemistry principles, by converting a waste stream into a high-value product, but also on the application of an approach following a circular economy model.
Keywords	Lactuca sativa ; alginates ; biomass ; circular economy ; encapsulation ; freeze drying ; green chemistry ; greenhouse experimentation ; greenhouses ; lettuce ; plant growth ; sewage sludge ; soil quality ; wastewater
Language	English
Dates of publication	2020-1201
Size	p. 277-285.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.07.097
Database	NAL-Catalogue (AGRICOLA)

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Article: Ascorbate Plus Buformin in AML: A Metabolic Targeted Treatment.

Banella, Cristina / Catalano, Gianfranco / Travaglini, Serena / Pelosi, Elvira / Ottone, Tiziana / Zaza, Alessandra / Guerrera, Gisella / Angelini, Daniela Francesca / Niscola, Pasquale / Divona, Mariadomenica / Battistini, Luca / Screnci, Maria / Ammatuna, Emanuele / Testa, Ugo / Nervi, Clara / Voso, Maria Teresa / Noguera, Nelida Ines

Cancers

2022 Volume 14, Issue 10

Abstract: In the present study, we characterized the metabolic background of different Acute Myeloid Leukemias' (AMLs) cells and described a heterogeneous and highly flexible energetic metabolism. Using the Seahorse XF Agilent, we compared the metabolism of normal ...

Abstract	In the present study, we characterized the metabolic background of different Acute Myeloid Leukemias' (AMLs) cells and described a heterogeneous and highly flexible energetic metabolism. Using the Seahorse XF Agilent, we compared the metabolism of normal hematopoietic progenitors with that of primary AML blasts and five different AML cell lines. We assessed the efficacy and mechanism of action of the association of high doses of ascorbate, a powerful oxidant, with the metabolic inhibitor buformin, which inhibits mitochondrial complex I and completely shuts down mitochondrial contributions in ATP production. Primary blasts from seventeen AML patients, assayed for annexin V and live/dead exclusion by flow cytometry, showed an increase in the apoptotic effect using the drug combination, as compared with ascorbate alone. We show that ascorbate inhibits glycolysis through interfering with HK1/2 and GLUT1 functions in hematopoietic cells. Ascorbate combined with buformin decreases mitochondrial respiration and ATP production and downregulates glycolysis, enhancing the apoptotic effect of ascorbate in primary blasts from AMLs and sparing normal CD34+ bone marrow progenitors. In conclusion, our data have therapeutic implications especially in fragile patients since both agents have an excellent safety profile, and the data also support the clinical evaluation of ascorbate-buformin in association with different mechanism drugs for the treatment of refractory/relapsing AML patients with no other therapeutic options.
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14102565
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Article: An Polycythemia Vera Evolve from Acute Myeloid Leukemia? Report of a Case Showing a Simultaneous Minor

Borsellino, Beatrice / Savi, Arianna / Pascale, Maria Rosaria / Meddi, Elisa / Del Principe, Maria Ilaria / Cristiano, Antonio / Ottone, Tiziana / Rapanotti, Maria Cristina / Divona, Mariadomenica / Travaglini, Serena / Attardi, Enrico / Palmieri, Raffaele / Buzzatti, Elisa / Buccisano, Francesco / Voso, Maria Teresa

Mediterranean journal of hematology and infectious diseases

2022 Volume 14, Issue 1, Page(s) e2022058

Abstract: The evolution of myeloproliferative neoplasms (MPN) to acute myeloid leukemia (AML) occurs in 2-10% of patients, depending on the MPN subtype, treatment, and follow-up length. The reverse-path from AML to MPN has been rarely reported. We herein present a ...

Abstract	The evolution of myeloproliferative neoplasms (MPN) to acute myeloid leukemia (AML) occurs in 2-10% of patients, depending on the MPN subtype, treatment, and follow-up length. The reverse-path from AML to MPN has been rarely reported. We herein present a 75 years old woman with AML, in whom a
Language	English
Publishing date	2022-07-01
Publishing country	Italy
Document type	Case Reports
ZDB-ID	2674750-9
ISSN	2035-3006
ISSN	2035-3006
DOI	10.4084/MJHID.2022.058
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