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  1. Article ; Online: Navigating the misty lands of monocytosis.

    Malcovati, Luca

    Blood

    2024  Volume 143, Issue 12, Page(s) 1062–1064

    MeSH term(s) Humans ; Leukocyte Disorders ; Leukocytosis ; World Health Organization
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023023332
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: VEXAS: walking on the edge of malignancy.

    Malcovati, Luca

    Blood

    2023  Volume 142, Issue 3, Page(s) 214–215

    MeSH term(s) Humans ; Clonal Hematopoiesis ; Neoplasms/therapy ; Walking
    Language English
    Publishing date 2023-11-27
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023020772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The journey of a thousand miles begins with 1 step.

    Malcovati, Luca

    Blood

    2021  Volume 138, Issue 10, Page(s) 824–826

    Language English
    Publishing date 2021-09-09
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021012304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Introduction.

    Malcovati, Luca

    Seminars in hematology

    2017  Volume 54, Issue 3, Page(s) 129–132

    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Editorial
    ZDB-ID 206923-4
    ISSN 1532-8686 ; 0037-1963
    ISSN (online) 1532-8686
    ISSN 0037-1963
    DOI 10.1053/j.seminhematol.2017.07.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: EHA Endorsement of the European Guidelines for Myelodysplastic Syndromes, MDS-RIGHT.

    Blum, Sabine / Malcovati, Luca

    HemaSphere

    2021  Volume 5, Issue 9, Page(s) e631

    Language English
    Publishing date 2021-08-30
    Publishing country United States
    Document type Editorial
    ISSN 2572-9241
    ISSN (online) 2572-9241
    DOI 10.1097/HS9.0000000000000631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Diagnosis and classification of myelodysplastic syndromes.

    Hasserjian, Robert P / Germing, Ulrich / Malcovati, Luca

    Blood

    2023  Volume 142, Issue 26, Page(s) 2247–2257

    Abstract: Abstract: Myelodysplastic syndromes (MDSs) are neoplastic myeloid proliferations characterized by ineffective hematopoiesis resulting in peripheral blood cytopenias. MDS is distinguished from nonneoplastic clonal myeloid proliferations by the presence ... ...

    Abstract Abstract: Myelodysplastic syndromes (MDSs) are neoplastic myeloid proliferations characterized by ineffective hematopoiesis resulting in peripheral blood cytopenias. MDS is distinguished from nonneoplastic clonal myeloid proliferations by the presence of morphologic dysplasia and from acute myeloid leukemia by a blast threshold of 20%. The diagnosis of MDS can be challenging because of the myriad other causes of cytopenias: accurate diagnosis requires the integration of clinical features with bone marrow and peripheral blood morphology, immunophenotyping, and genetic testing. MDS has historically been subdivided into several subtypes by classification schemes, the most recent of which are the International Consensus Classification and World Health Organization Classification (fifth edition), both published in 2022. The aim of MDS classification is to identify entities with shared genetic underpinnings and molecular pathogenesis, and the specific subtype can inform clinical decision-making alongside prognostic risk categorization. The current MDS classification schemes incorporate morphologic features (bone marrow and blood blast percentage, degree of dysplasia, ring sideroblasts, bone marrow fibrosis, and bone marrow hypocellularity) and also recognize 3 entities defined by genetics: isolated del(5q) cytogenetic abnormality, SF3B1 mutation, and TP53 mutation. It is anticipated that with advancing understanding of the genetic basis of MDS pathogenesis, future MDS classification will be based increasingly on genetic classes. Nevertheless, morphologic features in MDS reflect the phenotypic expression of the underlying abnormal genetic pathways and will undoubtedly retain importance to inform prognosis and guide treatment.
    MeSH term(s) Humans ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Bone Marrow/pathology ; Myeloproliferative Disorders/pathology ; Prognosis ; Leukemia, Myeloid, Acute/pathology
    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023020078
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

    Spinello, Angelo / Borišek, Jure / Malcovati, Luca / Magistrato, Alessandra

    International journal of molecular sciences

    2021  Volume 22, Issue 20

    Abstract: The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of ... ...

    Abstract The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long all-atom simulations addressed the binding/dissociation mechanism of H3B-8800 to wild type and K700E SF3B1-containing SF3b (
    MeSH term(s) Humans ; Molecular Dynamics Simulation ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Piperazines/chemistry ; Piperazines/metabolism ; Protein Conformation ; Pyridines/chemistry ; Pyridines/metabolism ; RNA Splicing ; RNA Splicing Factors/chemistry ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism
    Chemical Substances H3B-8800 ; Phosphoproteins ; Piperazines ; Pyridines ; RNA Splicing Factors ; SF3B1 protein, human
    Language English
    Publishing date 2021-10-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222011222
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Cannibalism by erythroleukaemic blasts.

    Travaglino, Erica / Malcovati, Luca

    British journal of haematology

    2018  Volume 183, Issue 1, Page(s) 14

    MeSH term(s) Blood Cell Count ; Cytophagocytosis ; Erythrocytes ; Humans ; Leukemia, Erythroblastic, Acute/pathology ; Leukocytes
    Language English
    Publishing date 2018-05-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.15422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Clonal hematopoiesis and myeloid malignancies: clonal dynamics and clinical implications.

    Elena, Chiara / Gallì, Anna / Bono, Elisa / Todisco, Gabriele / Malcovati, Luca

    Current opinion in hematology

    2021  Volume 28, Issue 5, Page(s) 347–355

    Abstract: Purpose of review: Clinical and experimental studies have uncovered relevant clinical implications of clonal hematopoiesis. However, the true magnitude of this process, clonal dynamics over time and mechanisms of progression into overt malignancy remain ...

    Abstract Purpose of review: Clinical and experimental studies have uncovered relevant clinical implications of clonal hematopoiesis. However, the true magnitude of this process, clonal dynamics over time and mechanisms of progression into overt malignancy remain to be largely elucidated. In this article, the consequences of clonal hematopoiesis, its significance in the context of cytopenia, and its implications in the clinical management of patients with myeloid malignancies are reviewed and discussed.
    Recent findings: Clonal hematopoiesis has been associated with higher risk of hematologic cancers, as well as of death from cardiovascular causes. Clonal hematopoiesis has been proven clinically relevant in the context of disorders characterized by peripheral blood cytopenia, including aplastic anemia, cytopenia of undetermined significance, as well as unexplained anemia of the elderly.
    Summary: The available evidence has been proving the utility of somatic mutational analysis in patients with unexplained cytopenia, as well as in those receiving a diagnosis of myeloid neoplasm, enabling more accurate diagnosis, risk assessment, effective therapeutic strategies and residual disease monitoring. The access to a minimally invasive assessment is paving the way for screening programs of clonal hematopoiesis in individuals with absent or mild hematologic phenotype, as well as for therapeutic targeting of preleukemia cells.
    MeSH term(s) Clonal Hematopoiesis ; Hematologic Neoplasms/etiology ; Hematologic Neoplasms/metabolism ; Hematologic Neoplasms/pathology ; Humans ; Myeloproliferative Disorders/etiology ; Myeloproliferative Disorders/metabolism ; Myeloproliferative Disorders/pathology ; Risk Factors
    Language English
    Publishing date 2021-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1153887-9
    ISSN 1531-7048 ; 1065-6251
    ISSN (online) 1531-7048
    ISSN 1065-6251
    DOI 10.1097/MOH.0000000000000675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3703: Show issues Location:
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  10. Article ; Online: IDH1-Mutant Preleukemic Hematopoietic Stem Cells Can Be Eliminated by Inhibition of Oxidative Phosphorylation.

    Landberg, Niklas / Köhnke, Thomas / Feng, Yang / Nakauchi, Yusuke / Fan, Amy C / Linde, Miles H / Karigane, Daiki / Lim, Kelly / Sinha, Rahul / Malcovati, Luca / Thomas, Daniel / Majeti, Ravindra

    Blood cancer discovery

    2024  , Page(s) OF1–OF18

    Abstract: Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at the time of acute myeloid leukemia (AML) diagnosis. pHSCs are the origin of leukemia and a potential reservoir for relapse. Using primary human ... ...

    Abstract Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at the time of acute myeloid leukemia (AML) diagnosis. pHSCs are the origin of leukemia and a potential reservoir for relapse. Using primary human samples and gene editing to model isocitrate dehydrogenase 1 (IDH1) mutant pHSCs, we show epigenetic, transcriptional, and metabolic differences between pHSCs and healthy hematopoietic stem cells (HSC). We confirm that IDH1-driven clonal hematopoiesis is associated with cytopenia, suggesting an inherent defect to fully reconstitute hematopoiesis. Despite giving rise to multilineage engraftment, IDH1-mutant pHSCs exhibited reduced proliferation, blocked differentiation, downregulation of MHC class II genes, and reprogramming of oxidative phosphorylation metabolism. Critically, inhibition of oxidative phosphorylation resulted in the complete eradication of IDH1-mutant pHSCs but not IDH2-mutant pHSCs or wild-type HSCs. Our results indicate that IDH1-mutant preleukemic clones can be targeted with complex I inhibitors, offering a potential strategy to prevent the development and relapse of leukemia.
    Significance: A high burden of pHSCs is associated with worse overall survival in AML. Using single-cell sequencing, metabolic assessment, and gene-edited human models, we find human pHSCs with IDH1 mutations to be metabolically vulnerable and sensitive to eradication by complex I inhibition. See related commentary by Steensma.
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3028898-8
    ISSN 2643-3249 ; 2643-3230
    ISSN (online) 2643-3249
    ISSN 2643-3230
    DOI 10.1158/2643-3230.BCD-23-0195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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