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  1. Article: History of Developing Acute Promyelocytic Leukemia Treatment and Role of Promyelocytic Leukemia Bodies.

    Bercier, Pierre / de Thé, Hugues

    Cancers

    2024  Volume 16, Issue 7

    Abstract: The story of acute promyelocytic leukemia (APL) discovery, physiopathology, and treatment is a unique journey, transforming the most aggressive form of leukemia to the most curable. It followed an empirical route fueled by clinical breakthroughs driving ... ...

    Abstract The story of acute promyelocytic leukemia (APL) discovery, physiopathology, and treatment is a unique journey, transforming the most aggressive form of leukemia to the most curable. It followed an empirical route fueled by clinical breakthroughs driving major advances in biochemistry and cell biology, including the discovery of PML nuclear bodies (PML NBs) and their central role in APL physiopathology. Beyond APL, PML NBs have emerged as key players in a wide variety of biological functions, including tumor-suppression and SUMO-initiated protein degradation, underscoring their broad importance. The APL story is an example of how clinical observations led to the incremental development of the first targeted leukemia therapy. The understanding of APL pathogenesis and the basis for cure now opens new insights in the treatment of other diseases, especially other acute myeloid leukemias.
    Language English
    Publishing date 2024-03-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16071351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The PML hub: An emerging actor of leukemia therapies.

    Rérolle, Domitille / de Thé, Hugues

    The Journal of experimental medicine

    2023  Volume 220, Issue 8

    Abstract: PML assembles into nuclear domains that have attracted considerable attention from cell and cancer biologists. Upon stress, PML nuclear bodies modulate sumoylation and other post-translational modifications, providing an integrated molecular framework ... ...

    Abstract PML assembles into nuclear domains that have attracted considerable attention from cell and cancer biologists. Upon stress, PML nuclear bodies modulate sumoylation and other post-translational modifications, providing an integrated molecular framework for the multiple roles of PML in apoptosis, senescence, or metabolism. PML is both a sensor and an effector of oxidative stress. Emerging data has demonstrated its key role in promoting therapy response in several hematological malignancies. While these membrane-less nuclear hubs can enforce efficient cancer cell clearance, their downstream pathways deserve better characterization. PML NBs are druggable and their known modulators may have broader clinical utilities than initially thought.
    MeSH term(s) Humans ; Leukemia ; Apoptosis ; Kinetics ; Oxidative Stress ; Protein Processing, Post-Translational
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20221213
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  3. Article ; Online: Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.

    Rérolle, Domitille / Wu, Hsin-Chieh / de Thé, Hugues

    Cold Spring Harbor perspectives in medicine

    2024  

    Abstract: Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration ... ...

    Abstract Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration can transform hematopoietic progenitors through the acquisition of dominant-negative properties toward both transcriptional control by nuclear receptors and PML-mediated senescence. The fortuitous identification of two drugs, arsenic trioxide (ATO) and all-
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a041582
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  4. Article ; Online: An exciting RXRA mutant revives interest in retinoids for acute myeloid leukemia.

    Qiu, Fang / De Thé, Hugues

    Haematologica

    2022  Volume 107, Issue 2, Page(s) 354–355

    MeSH term(s) Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Promyelocytic, Acute ; Retinoids/therapeutic use
    Chemical Substances Retinoids
    Language English
    Publishing date 2022-02-01
    Publishing country Italy
    Document type Journal Article ; Comment
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2021.279152
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  5. Article ; Online: Sumoylation in Physiology, Pathology and Therapy.

    Sahin, Umut / de Thé, Hugues / Lallemand-Breitenbach, Valérie

    Cells

    2022  Volume 11, Issue 5

    Abstract: Sumoylation is an essential post-translational modification that has evolved to regulate intricate networks within emerging complexities of eukaryotic cells. Thousands of target substrates are modified by SUMO peptides, leading to changes in protein ... ...

    Abstract Sumoylation is an essential post-translational modification that has evolved to regulate intricate networks within emerging complexities of eukaryotic cells. Thousands of target substrates are modified by SUMO peptides, leading to changes in protein function, stability or localization, often by modulating interactions. At the cellular level, sumoylation functions as a key regulator of transcription, nuclear integrity, proliferation, senescence, lineage commitment and stemness. A growing number of prokaryotic and viral proteins are also emerging as prime sumoylation targets, highlighting the role of this modification during infection and in immune processes. Sumoylation also oversees epigenetic processes. Accordingly, at the physiological level, it acts as a crucial regulator of development. Yet, perhaps the most prominent function of sumoylation, from mammals to plants, is its role in orchestrating organismal responses to environmental stresses ranging from hypoxia to nutrient stress. Consequently, a growing list of pathological conditions, including cancer and neurodegeneration, have now been unambiguously associated with either aberrant sumoylation of specific proteins and/or dysregulated global cellular sumoylation. Therapeutic enforcement of sumoylation can also accomplish remarkable clinical responses in various diseases, notably acute promyelocytic leukemia (APL). In this review, we will discuss how this modification is emerging as a novel drug target, highlighting from the perspective of translational medicine, its potential and limitations.
    MeSH term(s) Animals ; Mammals/metabolism ; Plants/metabolism ; Protein Processing, Post-Translational ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation ; Viral Proteins/metabolism
    Chemical Substances Small Ubiquitin-Related Modifier Proteins ; Viral Proteins
    Language English
    Publishing date 2022-02-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11050814
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  6. Article ; Online: In APL, noncoding mutations and SNP converge on WT1.

    Wu, Hsin-Chieh / de Thé, Hugues

    Blood

    2022  Volume 140, Issue 10, Page(s) 1060–1061

    MeSH term(s) Germ Cells ; Humans ; Leukemia, Promyelocytic, Acute/genetics ; Mutation ; WT1 Proteins/genetics
    Chemical Substances WT1 Proteins ; WT1 protein, human
    Language English
    Publishing date 2022-09-08
    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.2022017214
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  7. Article ; Online: Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-κB activation and survival.

    Hleihel, Rita / Skayneh, Hala / de Thé, Hugues / Hermine, Olivier / Bazarbachi, Ali

    Blood cancer journal

    2023  Volume 13, Issue 1, Page(s) 67

    Abstract: Adult T cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with human T cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax initiates T cell transformation through activation of critical cellular pathways, ... ...

    Abstract Adult T cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with human T cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax initiates T cell transformation through activation of critical cellular pathways, including NF-κB. Unexpectedly, Tax protein is not detectable in most ATL cells, in contrast to the HTLV-1 HBZ protein which antagonizes Tax effects. Here, we demonstrate that primary ATL cells from patients with acute or chronic ATL express very low levels of Tax mRNA and protein. Critically, survival of these primary ATL cells is dependent on continued Tax expression. Mechanistically, Tax extinction results in reversal of NF-κB activation, P53/PML activation and apoptosis. Tax drives interleukin-10 (IL-10) expression and recombinant IL-10 rescues the survival of tax-depleted primary ATL cells. These results demonstrate the critical role of continued Tax and IL-10 expression for the survival of primary ATL cells, highlighting their relevance as therapeutic targets.
    MeSH term(s) Adult ; Humans ; Human T-lymphotropic virus 1 ; Leukemia-Lymphoma, Adult T-Cell/pathology ; NF-kappa B/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Lymphoma
    Chemical Substances NF-kappa B ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2023-05-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-023-00841-7
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  8. Article ; Online: Differentiation therapy revisited.

    de Thé, Hugues

    Nature reviews. Cancer

    2017  Volume 18, Issue 2, Page(s) 117–127

    Abstract: The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic ... ...

    Abstract The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal. By reviewing other successful examples of drug-induced tumour cell differentiation, novel approaches to transform differentiating drugs into more efficient therapies are proposed.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Arsenic Trioxide/therapeutic use ; Cell Differentiation/drug effects ; Humans ; Leukemia, Promyelocytic, Acute/drug therapy ; Leukemia, Promyelocytic, Acute/physiopathology ; Tretinoin/therapeutic use
    Chemical Substances Antineoplastic Agents ; Tretinoin (5688UTC01R) ; Arsenic Trioxide (S7V92P67HO)
    Language English
    Publishing date 2017-12-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/nrc.2017.103
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    Zs.A 5563: Show issues Location:
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  9. Article ; Online: PML/RARα Destabilization by Hyperthermia: A New Model for Oncogenic Fusion Protein Degradation?

    Wu, Hsin Chieh / Rérolle, Domitille / de Thé, Hugues

    Cancer discovery

    2021  Volume 2, Issue 4, Page(s) 300–301

    Abstract: In this issue, Maimaitiyiming and colleagues demonstrate thermic stress-induced PML/RARα oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARα degradation by arsenic trioxide (ATO) and may ... ...

    Abstract In this issue, Maimaitiyiming and colleagues demonstrate thermic stress-induced PML/RARα oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARα degradation by arsenic trioxide (ATO) and may circumvent ATO-resistance in historic acute promyelocytic leukemia patients. This novel approach could be extended to other corepressor-associated oncogenic fusion proteins.
    Language English
    Publishing date 2021-05-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2643-3230.BCD-21-0071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6916: Show issues Location:
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  10. Article ; Online: PML/RARA destabilization by hyperthermia: a new model for oncogenic fusion protein degradation?

    Wu, Hsin Chieh / Rérolle, Domitille / de Thé, Hugues

    Blood cancer discovery

    2021  Volume 2, Issue 4, Page(s) 300–301

    Abstract: In this issue, Maimaitiyiming and colleagues demonstrate thermic stress-induced PML/RARA oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARA degradation by ATO and may circumvent ATO- ... ...

    Abstract In this issue, Maimaitiyiming and colleagues demonstrate thermic stress-induced PML/RARA oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARA degradation by ATO and may circumvent ATO-resistance in historical APL patients. This novel approach could be extended to other corepressor-associated oncogenic fusion proteins.
    MeSH term(s) Arsenic Trioxide ; Arsenicals/pharmacology ; Humans ; Hyperthermia, Induced ; Leukemia, Promyelocytic, Acute/metabolism ; Oxides/pharmacology ; Proteolysis
    Chemical Substances Arsenicals ; Oxides ; Arsenic Trioxide (S7V92P67HO)
    Language English
    Publishing date 2021-07-06
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 3028898-8
    ISSN 2643-3249 ; 2643-3230
    ISSN (online) 2643-3249
    ISSN 2643-3230
    DOI 10.1158/2643-3230.BCD-21-0071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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